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Molecules, Volume 21, Issue 2 (February 2016)

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Open AccessArticle Functional Characterization of a Dihydroflavanol 4-Reductase from the Fiber of Upland Cotton (Gossypium hirsutum)
Molecules 2016, 21(2), 32; doi:10.3390/molecules21020032
Received: 30 September 2015 / Revised: 10 December 2015 / Accepted: 21 December 2015 / Published: 26 January 2016
Cited by 3 | PDF Full-text (5254 KB) | HTML Full-text | XML Full-text
Abstract
Dihydroflavanol 4-reductase (DFR) is a key later enzyme involved in two polyphenols’ (anthocyanins and proanthocyanidins (PAs)) biosynthesis, however it is not characterized in cotton yet. In present reports, a DFR cDNA homolog (designated as GhDFR1) was cloned from developing fibers of upland
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Dihydroflavanol 4-reductase (DFR) is a key later enzyme involved in two polyphenols’ (anthocyanins and proanthocyanidins (PAs)) biosynthesis, however it is not characterized in cotton yet. In present reports, a DFR cDNA homolog (designated as GhDFR1) was cloned from developing fibers of upland cotton. Silencing GhDFR1 in cotton by virus-induced gene silencing led to significant decrease in accumulation of anthocyanins and PAs. More interestingly, based on LC-MS analysis, two PA monomers, (–)-epicatachin and (–)-epigallocatachin, remarkably decreased in content in fibers of GhDFR1-silenced plants, but two new monomers, (–)-catachin and (–)-gallocatachin were present compared to the control plants infected with empty vector. The ectopic expression of GhDFR1 in an Arabidopsis TT3 mutant allowed for reconstruction of PAs biosynthesis pathway and led to accumulation of PAs in seed coat. Taken together, these data demonstrate that GhDFR1 contributes to the biosynthesis of anthocyanins and PAs in cotton. Full article
(This article belongs to the Special Issue Recent Advances in Plant Phenolics)
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Open AccessArticle Quality Evaluation of Traditional Chinese Medicine Compounds in Xiaoyan Lidan Tablets: Fingerprint and Quantitative Analysis Using UPLC-MS
Molecules 2016, 21(2), 83; doi:10.3390/molecules21020083
Received: 16 November 2015 / Revised: 21 December 2015 / Accepted: 5 January 2016 / Published: 22 January 2016
Cited by 3 | PDF Full-text (1526 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
XiaoyanLidan tablets (XYLDTs) are traditional Chinese medicines frequently used for syndromes of the liver and gallbladder, cholecystitis and cholangitis. To evaluate the consistency of the quality of commercial XYLDT preparations, we established a simple and reliable ultra-performance liquid chromatography (UPLC) method with a
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XiaoyanLidan tablets (XYLDTs) are traditional Chinese medicines frequently used for syndromes of the liver and gallbladder, cholecystitis and cholangitis. To evaluate the consistency of the quality of commercial XYLDT preparations, we established a simple and reliable ultra-performance liquid chromatography (UPLC) method with a photodiode array (PDA) detector and mass spectrometry (MS), including a fingerprint analysis and quantification of the main pharmacologically-active markers. In the UPLC-PDA detection-based fingerprint analysis of XYLDTs, approximately 39 peaks were found in the XYLDT chromatogram, 26 of which were attributed to Picrasmaquassioides, nine to Andrographis and four to Isodonserra. Subsequently, the structures of these bioactive markers were identified through ESI-MS analyses. Using the chemometricmethods of similarity analysis and principal component analysis, the five significant herbal componentswere determined as 4-methoxy-5-hydroxycanthin-6-one, andrographolide, dehydroandrographolide, neoandrographolide and rosmarinic acid, and these components were qualitatively assessed. Our experimental results demonstrated that combining the fingerprint analysis with UPLC-MS and multi-ingredient determination is useful for rapid pharmaceutical quality evaluation. Moreover, the combined approach can potentially differentiate the origin, determine the authenticity and assess the overall quality of the formulae. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6-di(CH2OH)py)2]NO3
Molecules 2016, 21(2), 87; doi:10.3390/molecules21020087
Received: 17 December 2015 / Revised: 2 January 2016 / Accepted: 6 January 2016 / Published: 28 January 2016
Cited by 7 | PDF Full-text (3328 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922
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Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44–28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle New α-Methylene-γ-Butyrolactone Derivatives as Potential Fungicidal Agents: Design, Synthesis and Antifungal Activities
Molecules 2016, 21(2), 130; doi:10.3390/molecules21020130
Received: 10 December 2015 / Revised: 18 January 2016 / Accepted: 19 January 2016 / Published: 22 January 2016
Cited by 3 | PDF Full-text (1832 KB) | HTML Full-text | XML Full-text
Abstract
In consideration of the fact that the α-methylene-γ-butyrolactone moiety is a major bio-functional group in the structure of carabrone and possesses some agricultural biological activity, forty-six new ester and six new ether derivatives containing α-methylene-γ-butyrolactone moieties were synthesized, and their fungicidal activities against
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In consideration of the fact that the α-methylene-γ-butyrolactone moiety is a major bio-functional group in the structure of carabrone and possesses some agricultural biological activity, forty-six new ester and six new ether derivatives containing α-methylene-γ-butyrolactone moieties were synthesized, and their fungicidal activities against Colletotrichum lagenarium and Botrytis cinerea were investigated. Most of the synthesized compounds showed moderate to significant fungicidal activity. Among them, halogen atom-containing derivatives showed better activity than others, especially compounds 6a,d which exhibited excellent fungicidal activity against C. lagenarium, with IC50 values of 7.68 and 8.17 μM. The structure-activity relationship (SAR) analysis indicated that ester derivatives with electron-withdrawing groups on the benzene ring showed better fungicidal activity than those with electron-donating groups. A quantitative structure-activity relationship (QSAR) model (R2 = 0.9824, F = 203.01, S2 = 0.0083) was obtained through the heuristic method. The built model revealed a strong correlation of fungicidal activity against C. lagenarium with the molecular structures of these compounds. These results are expected to prove helpful in the design and exploration of low toxicity and high efficiency α-methylene-γ-butyrolactone-based fungicides. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Graveoline Analogs Exhibiting Selective Acetylcholinesterase Inhibitory Activity as Potential Lead Compounds for the Treatment of Alzheimer’s Disease
Molecules 2016, 21(2), 132; doi:10.3390/molecules21020132
Received: 11 December 2015 / Revised: 18 January 2016 / Accepted: 20 January 2016 / Published: 22 January 2016
Cited by 2 | PDF Full-text (2471 KB) | HTML Full-text | XML Full-text
Abstract
This study designed and synthesized a series of new graveoline analogs on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of these analogs was also evaluated. Results showed that the synthesized graveoline analogs displayed stronger inhibitory activity against
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This study designed and synthesized a series of new graveoline analogs on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of these analogs was also evaluated. Results showed that the synthesized graveoline analogs displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (Selectivity Index from 45 to 486). When the two sites in the graveoline parent ring substituting phenyl and amino terminal had six chemical bonds (n = 3) and the terminal amino was piperidine, compound 5c showed the best activity. Furthermore, the mechanism of action and binding mode were explored by enzyme kinetic simulation, molecular docking, and thioflavin T-based fluorometric assay. Cytotoxicity assay showed that the low concentration of the analogs did not affect the viability of the neurocyte SH-SY5Y. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
Open AccessArticle Protective Effect of Cleistocalyx nervosum var. paniala Fruit Extract against Oxidative Renal Damage Caused by Cadmium
Molecules 2016, 21(2), 133; doi:10.3390/molecules21020133
Received: 29 November 2015 / Revised: 17 January 2016 / Accepted: 19 January 2016 / Published: 22 January 2016
Cited by 4 | PDF Full-text (1567 KB) | HTML Full-text | XML Full-text
Abstract
Cadmium nephrotoxicity is a serious environmental health problem as it will eventually end up with end stage renal disease. The pathobiochemical mechanism of this toxic heavy metal is related to oxidative stress. This study investigated whether Cleistocalyx nervosum var. paniala fruit extract (CNFE)
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Cadmium nephrotoxicity is a serious environmental health problem as it will eventually end up with end stage renal disease. The pathobiochemical mechanism of this toxic heavy metal is related to oxidative stress. This study investigated whether Cleistocalyx nervosum var. paniala fruit extract (CNFE) could protect the kidney against oxidative injury caused by cadmium. Initial analysis of the extract revealed antioxidant abilities and high levels of polyphenols, particularly catechin. Its potential renal benefits was further explored in rats treated with vehicle, CNFE, cadmium (2 mg/kg), and cadmium plus CNFE (0.5, 1, 2 g/kg) for four weeks. Oxidative renal injury was developed after cadmium exposure as evidenced by blood urea nitrogen and creatinine retention, glomerular filtration reduction, renal structural damage, together with increased nitric oxide and malondialdehyde, but decreased antioxidant thiols, superoxide dismutase, and catalase in renal tissues. Cadmium-induced nephrotoxicity was diminished in rats supplemented with CNFE, particularly at the doses of 1 and 2 g/kg. It is concluded that CNFE is able to protect against the progression of cadmium nephrotoxicity, mostly via its antioxidant power. The results also point towards a promising role for this naturally-occurring antioxidant to combat other human disorders elicited by disruption of redox homeostasis. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle The Blood-Brain Barrier Permeability of Lignans and Malabaricones from the Seeds of Myristica fragrans in the MDCK-pHaMDR Cell Monolayer Model
Molecules 2016, 21(2), 134; doi:10.3390/molecules21020134
Received: 17 December 2015 / Revised: 15 January 2016 / Accepted: 19 January 2016 / Published: 22 January 2016
Cited by 6 | PDF Full-text (1328 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp
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The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10−8–10−6 cm/s; those of 8-O-4′-neolignan and tetrahydrofuran-lignan were at 10−6–10−5 cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10−8–10−7 cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Coumarins as Potential Antioxidant Agents Complemented with Suggested Mechanisms and Approved by Molecular Modeling Studies
Molecules 2016, 21(2), 135; doi:10.3390/molecules21020135
Received: 5 December 2015 / Revised: 8 January 2016 / Accepted: 19 January 2016 / Published: 23 January 2016
Cited by 8 | PDF Full-text (2109 KB) | HTML Full-text | XML Full-text
Abstract
Syntheses of coumarins, which are a structurally interesting antioxidant activity, was done in this article. The modification of 7-hydroxycoumarin by different reaction steps was done to yield target compounds. Molecular structures were characterized by different spectroscopical techniques (Fourier transformation infrared and nuclear magnetic
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Syntheses of coumarins, which are a structurally interesting antioxidant activity, was done in this article. The modification of 7-hydroxycoumarin by different reaction steps was done to yield target compounds. Molecular structures were characterized by different spectroscopical techniques (Fourier transformation infrared and nuclear magnetic resonance). Antioxidant activities were performed by using various in vitro spectrophometric assays against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and hydrogen peroxide (H2O2). All compounds exhibited high efficiency as antioxidants compared to ascorbic acid. The highest efficiency scavenging activity was found for compound 3 (91.0 ± 5.0), followed by compounds 2 and 4 (88.0 ± 2.00; and 87.0 ± 3.00). Ascorbic acid C was used as a standard drug with a percentage inhibition of 91.00 ± 1.5. The mechanism of the synthesized compounds as antioxidants was also studied. Hartree–Fock–based quantum chemical studies have been carried out with the basis set to 3-21G, in order to obtain information about the three-dimensional (3D) geometries, electronic structure, molecular modeling, and electronic levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), to understand the antioxidant activity for the synthesized compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle The Inhibitory Mechanisms Study of 5,6,4′-Trihydroxy-7,3′-Dimethoxyflavone against the LPS-Induced Macrophage Inflammatory Responses through the Antioxidant Ability
Molecules 2016, 21(2), 136; doi:10.3390/molecules21020136
Received: 2 December 2015 / Revised: 14 January 2016 / Accepted: 18 January 2016 / Published: 22 January 2016
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Abstract
The whole plant of Anisomeles ovata has been widely used in Taiwan for treating inflammation-related skin and liver diseases, however, the detailed pharmacology mechanisms have yet to be elucidated. In the present study, one of the major components, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (5-TDMF), was purified from
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The whole plant of Anisomeles ovata has been widely used in Taiwan for treating inflammation-related skin and liver diseases, however, the detailed pharmacology mechanisms have yet to be elucidated. In the present study, one of the major components, 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (5-TDMF), was purified from a methanol extract of Anisomeles ovata. A pharmacological study of this compound suggests that 5-TDMF possesses potent free radical scavenging activity both in vitro and ex vivo. Furthermore, 5-TDMF reduces nitric oxide and pro-inflammatory cytokine production in LPC-treated RAW 264.7 cells through the attenuation of nitric oxide synthase and cyclooxygenase-2. Additional experiments suggest that of 5-TDMF interferes with nuclear factor-κB translocation and mitogen-activated protein kinase pathways. These results identify 5-TDMF as an anti-oxidant and anti-inflammatory compound, explain the pharmacologic function of Anisomeles ovata and suggest its great potential as a new anti-inflammatory remedy. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antiproliferative Effects of New Dimeric Ellagitannin from Cornus alba in Prostate Cancer Cells Including Apoptosis-Related S-Phase Arrest
Molecules 2016, 21(2), 137; doi:10.3390/molecules21020137
Received: 5 January 2016 / Revised: 16 January 2016 / Accepted: 18 January 2016 / Published: 23 January 2016
Cited by 1 | PDF Full-text (1166 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13), together with 12 known compounds. The known compounds included four
[...] Read more.
Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13), together with 12 known compounds. The known compounds included four flavonoids (catechin (1), quercetin-3-O-β-d-glucuronide (2), quercetin-3-O-β-d-glucopyranoside (3), kaempferol-3-O-β-d-glucopyranoside (4)) and eight hydrolysable tannins (gallic acid (5), 2,6-di-O-galloyl-hamamelofuranoside (6), 2-galloyl-4-caffeoyl-l-threonic acid (7) 2,3-di-O-galloyl-4-caffeoyl-l-threonic acid (8), 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (9), cornusiin B (10), cornusiin A (11) and camptothin B (12)). All compounds exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity. Especially, the radical scavenging activities of 6 and 913 were higher than that of vitamin C. Compounds 9, 11, 12 and 13 inhibited the production of nitric oxide (NO) in lipopolysaccharide-stimulated RAW264.7 cells to the same degree as NG-Monomethyl-l-arginine (l-NMMA). When the antiproliferative effects of the isolated compounds were assessed in prostate cancer cells, the dimeric ellagitannins (1113) selectively inhibited LNCaP hormone-dependent prostate cancer cells. Flow cytometry analysis indicated that the dimeric ellagitannins induced apoptosis and S-phase arrest. These results suggest that dimeric ellagitannins from Cornus alba can be developed as functional materials or herbal medicines for prostate tumors such as benign prostate hyperplasia and early-stage prostate cancer. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Antioxidant Activity of 3-[N-(Acylhydrazono)ethyl]-4-hydroxy-coumarins
Molecules 2016, 21(2), 138; doi:10.3390/molecules21020138
Received: 27 October 2015 / Revised: 29 December 2015 / Accepted: 15 January 2016 / Published: 23 January 2016
Cited by 4 | PDF Full-text (1228 KB) | HTML Full-text | XML Full-text
Abstract
A series of 3-acylhydrazono-4-hydroxycoumarins were synthesized via condensation of 3-acetyl-4-hydroxycoumarin with appropriate hydrazides. The structures of the newly-synthesized compounds were characterized by spectral and elememental analysis or HRMS measurements. Their antioxidant properties were evaluated by using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as
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A series of 3-acylhydrazono-4-hydroxycoumarins were synthesized via condensation of 3-acetyl-4-hydroxycoumarin with appropriate hydrazides. The structures of the newly-synthesized compounds were characterized by spectral and elememental analysis or HRMS measurements. Their antioxidant properties were evaluated by using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as inhibition of lipid peroxidation. Moreover, their ability to inhibit in vitro soybean lipoxygenase has been investigated. They were found to be capable of rapid inactivation of alkylperoxy radicals. Full article
(This article belongs to the Special Issue Antioxidants—A Risk-Benefit Analysis for Health)
Open AccessArticle Antibacterial and Synergistic Activity of Pentacyclic Triterpenoids Isolated from Alstonia scholaris
Molecules 2016, 21(2), 139; doi:10.3390/molecules21020139
Received: 24 December 2015 / Revised: 12 January 2016 / Accepted: 21 January 2016 / Published: 25 January 2016
Cited by 8 | PDF Full-text (662 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
(1) Background: Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in “Dai” ethnopharmacy to treat infectious diseases in China. Although various pharmacological activities have been reported, the antimicrobial constitutes of A. scholaris have not yet been identified. The
[...] Read more.
(1) Background: Alstonia scholaris (Apocynaceae) is an important medicinal plant that has been historically used in “Dai” ethnopharmacy to treat infectious diseases in China. Although various pharmacological activities have been reported, the antimicrobial constitutes of A. scholaris have not yet been identified. The objective of this study is to evaluate the antibacterial constitutes from the leaf extract of A. scholaris and to assess the synergistic effects of isolated compounds with antibiotics against bacterial pathogens.; (2) Methods: The chemical constitutes isolated from the leaf extract of A. scholaris were structurally identified by NMR. The antibacterial and synergistic effect of compounds was assessed by calculating the minimal inhibitory concentration (MIC), checkerboard dilution test, and time-kill assay.; (3) Results: Six pentacyclic triterpenoids were structurally identified as (1) lupeol, (2) betulin, (3) 3-hydroxy-11-ursen-28,13-olide, (4) betulinic acid, (5) oleanolic acid and (6) ursolic acid. Both oleanolic and ursolic acid showed antibacterial activity but were limited to Gram-positive bacteria. Ursolic acid showed a synergistic effect with ampicillin and tetracycline against both Bacillus cereus and S. aureus.; (4) Conclusion: These findings reflect that pentacyclic triterpenoids are the antibacterial chemicals in A. scholaris. The ability of ursolic acid to enhance the activity of antibiotics can constitute a valuable group of therapeutic agents in the future. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Miracle Fruit (Synsepalum dulcificum) Exhibits as a Novel Anti-Hyperuricaemia Agent
Molecules 2016, 21(2), 140; doi:10.3390/molecules21020140
Received: 31 December 2015 / Revised: 15 January 2016 / Accepted: 20 January 2016 / Published: 26 January 2016
Cited by 2 | PDF Full-text (3182 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects.
[...] Read more.
Miracle fruit (Synsepalum dulcificum) belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA), and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU)-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Detecting β-Casein Variation in Bovine Milk
Molecules 2016, 21(2), 141; doi:10.3390/molecules21020141
Received: 25 November 2015 / Revised: 30 December 2015 / Accepted: 18 January 2016 / Published: 25 January 2016
Cited by 1 | PDF Full-text (1336 KB) | HTML Full-text | XML Full-text
Abstract
In bovine species, β-casein (β-CN) is characterized by genetic polymorphism. The two most common protein variants are β-CN A2 (the original one) and A1, differing from A2 for one amino acid substitution (Pro67 to His67). Several
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In bovine species, β-casein (β-CN) is characterized by genetic polymorphism. The two most common protein variants are β-CN A2 (the original one) and A1, differing from A2 for one amino acid substitution (Pro67 to His67). Several bioactive peptides affecting milk nutritional properties can originate from β-CN. Among them, β-casomorphin-7 (BCM7) ranging from amino acid 60 to 66 can be released more easily from β-CN variants carrying His67 (A1 type) instead of Pro67 (A2 type). Nowadays, “A2 milk” is produced in different countries claiming its potential benefits in human health. The aim of this study was to further develop and apply an isoelectric focusing electrophoresis (IEF) method to bulk and individual milk samples in order to improve its use for β-CN studies. We succeeded in identifying A2 milk samples correctly and quantifying the percentage of A2, A1, and B variants in bulk samples not derived from A2 milk as well as in individual milk samples. The method allows us to quantify the relative proportion of β-CN variants in whole milk without eliminating whey protein by acid or enzymatic precipitation of caseins. The aim of this study was also to study the different behavior of β-CN and β-lactoglobulin (β-LG) in the presence of trichloroacetic acid (TCA). The higher sensitivity of β-CN to TCA allows quantifying β-CN variants after TCA fixation because β-LG is not visible. Monitoring β-CN variation in cattle breeds is important in order to maintain a certain balance between Pro67 and His67 in dairy products. Overall, the debate between A1 and A2 milk needs further investigation. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract
Molecules 2016, 21(2), 143; doi:10.3390/molecules21020143
Received: 15 November 2015 / Revised: 14 January 2016 / Accepted: 20 January 2016 / Published: 26 January 2016
Cited by 3 | PDF Full-text (1125 KB) | HTML Full-text | XML Full-text
Abstract
The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded
[...] Read more.
The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of α-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited α-crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of α-crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on α-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract. Full article
Open AccessArticle Evaluation of Functionality and Biological Responses of Mytilus galloprovincialis after Exposure to Quaternium-15 (Methenamine 3-Chloroallylochloride)
Molecules 2016, 21(2), 144; doi:10.3390/molecules21020144
Received: 20 November 2015 / Revised: 11 January 2016 / Accepted: 20 January 2016 / Published: 26 January 2016
Cited by 23 | PDF Full-text (890 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Although the irritant effects of quaternium-15 have been established, little is known about the toxicological consequences induced by this xenobiotic on aquatic invertebrates. The present article reports toxicological, histological and physiological effects of quaternium-15 following the exposure of Mytilus galloprovincialis for 18 days
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Although the irritant effects of quaternium-15 have been established, little is known about the toxicological consequences induced by this xenobiotic on aquatic invertebrates. The present article reports toxicological, histological and physiological effects of quaternium-15 following the exposure of Mytilus galloprovincialis for 18 days at three different concentrations (0.1, 1.0 and 2.0 mg/L). The results demonstrate that at higher concentrations histological damages to M. galloprovincialis gills occur, like melanosis, light exfoliations, increase of mucus production and infiltrative inflammation. In addition digestive gland cells of M. galloprovincialis, were not able to perform the regulation volume decrease (RVD) owing to osmotic stress following the exposure to the preservative. Overall, this first study on quaternium-15 highlights that it can jeopardize both the morphology and vital physiological processes in marine invertebrates, depending on the duration of exposure and the concentration of the preservative, indicating that further studies are necessary to increase our knowledge about the effects of this substance, commonly added to our products of daily use. Full article
Open AccessCommunication Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents
Molecules 2016, 21(2), 145; doi:10.3390/molecules21020145
Received: 20 November 2015 / Revised: 11 January 2016 / Accepted: 20 January 2016 / Published: 26 January 2016
Cited by 4 | PDF Full-text (649 KB) | HTML Full-text | XML Full-text
Abstract
In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using 1H-NMR, 13C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results
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In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using 1H-NMR, 13C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 µM to AGS, 4.4 µM to HT-29 cells and 5.8 µM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 µM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) Copper Complex Grafted Solid Catalyst for Oxidative Polymerization of 2,6-Dimethylphenol
Molecules 2016, 21(2), 146; doi:10.3390/molecules21020146
Received: 6 October 2015 / Revised: 18 January 2016 / Accepted: 21 January 2016 / Published: 26 January 2016
Cited by 1 | PDF Full-text (915 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new solid phase catalyst, poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) copper(I) complex, grafted onto polystyrene particles, has been employed for the oxidative polymerization of 2,6-dimethylphenol using an aqueous biphasic (water/toluene) solvent system. The solid catalyst was synthesized by first grafting N-(4-vinylbenzyl)-1,4,7-triaza-cyclononane onto polystyrene particles
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A new solid phase catalyst, poly(N-4-vinylbenzyl-1,4,7-triazacyclononane) copper(I) complex, grafted onto polystyrene particles, has been employed for the oxidative polymerization of 2,6-dimethylphenol using an aqueous biphasic (water/toluene) solvent system. The solid catalyst was synthesized by first grafting N-(4-vinylbenzyl)-1,4,7-triaza-cyclononane onto polystyrene particles using a radical mediated polymerization method and next by creating the polymer-metal complex of copper-triazacyclononane with these modified particles. Poly(2,6-dimethyl-1,4-phenylene oxide) was successfully obtained from the polymerization of 2,6-dimethylphenol using this new metal-organic solid phase catalyst. Full article
(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)
Open AccessArticle Coumarin-Containing Polymers for High Density Non-Linear Optical Data Storage
Molecules 2016, 21(2), 147; doi:10.3390/molecules21020147
Received: 8 December 2015 / Revised: 7 January 2016 / Accepted: 18 January 2016 / Published: 26 January 2016
Cited by 5 | PDF Full-text (1806 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Optical data storage was performed with various thin polymer films containing coumarin-based derivatives and by using femtosecond laser pulses as well as two-photon absorption processes. Exploring the photodimerization attribute of coumarin derivatives and using appropriate irradiation wavelengths, recording/erasing processes could be carried out
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Optical data storage was performed with various thin polymer films containing coumarin-based derivatives and by using femtosecond laser pulses as well as two-photon absorption processes. Exploring the photodimerization attribute of coumarin derivatives and using appropriate irradiation wavelengths, recording/erasing processes could be carried out in the same area. Second harmonic generation microscopy was used to read the stored information. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle A SILAC-Based Approach Elicits the Proteomic Responses to Vancomycin-Associated Nephrotoxicity in Human Proximal Tubule Epithelial HK-2 Cells
Molecules 2016, 21(2), 148; doi:10.3390/molecules21020148
Received: 18 December 2015 / Revised: 14 January 2016 / Accepted: 15 January 2016 / Published: 29 January 2016
Cited by 5 | PDF Full-text (9772 KB) | HTML Full-text | XML Full-text
Abstract
Vancomycin, a widely used antibiotic, often induces nephrotoxicity, however, the molecular targets and underlying mechanisms of this side effect remain unclear. The present study aimed to examine molecular interactome and analyze the signaling pathways related to the vancomycin-induced nephrotoxicity in human proximal tubule
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Vancomycin, a widely used antibiotic, often induces nephrotoxicity, however, the molecular targets and underlying mechanisms of this side effect remain unclear. The present study aimed to examine molecular interactome and analyze the signaling pathways related to the vancomycin-induced nephrotoxicity in human proximal tubule epithelial HK-2 cells using the stable isotope labeling by amino acids in cell culture (SILAC) approach. The quantitative proteomic study revealed that there were at least 492 proteins interacting with vancomycin and there were 290 signaling pathways and cellular functions potentially regulated by vancomycin in HK-2 cells. These proteins and pathways played a critical role in the regulation of cell cycle, apoptosis, autophagy, EMT, and ROS generation. These findings suggest that vancomycin-induced proteomic responses in HK-2 cells involvefunctional proteins and pathways that regulate cell cycle, apoptosis, autophagy, and redox homeostasis. This is the first systemic study revealed the networks of signaling pathways and proteomic responses to vancomycin treatment in HK-2 cells, and the data may be used to discriminate the molecular and clinical subtypes and to identify new targets and biomarkers for vancomycin-induced nephrotoxic effect. Further studies are warranted to explore the potential of quantitative proteomic analysis in the identification of new targets and biomarkers for drug-induced renal toxicity. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
Open AccessArticle Metabolite Profiling Reveals the Effect of Dietary Rubus coreanus Vinegar on Ovariectomy-Induced Osteoporosis in a Rat Model
Molecules 2016, 21(2), 149; doi:10.3390/molecules21020149
Received: 10 December 2015 / Revised: 15 January 2016 / Accepted: 21 January 2016 / Published: 26 January 2016
Cited by 6 | PDF Full-text (1916 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats,
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The study was aimed at exploring the curative effects of Rubus coreanus (RC) vinegar against postmenopausal osteoporosis by using ovariectomized rats as a model. The investigations were performed in five groups: sham, ovariectomized (OVX) rats without treatment, low-dose RC vinegar (LRV)-treated OVX rats, high-dose RC vinegar (HRV)-treated OVX rats and alendronate (ALEN)-treated OVX rats. The efficacy of RC vinegar was evaluated using physical, biochemical, histological and metabolomic parameters. Compared to the OVX rats, the LRV and HRV groups showed positive effects on the aforementioned parameters, indicating estrogen regulation. Plasma metabolome analysis of the groups using gas chromatography-time of flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole-TOF-MS (UPLC-Q-TOF-MS) with multivariate analysis revealed 19 and 16 metabolites, respectively. Notably, the levels of butyric acid, phenylalanine, glucose, tryptophan and some lysophosphatidylcholines were marginally increased in RC vinegar-treated groups compared to OVX. However, the pattern of metabolite levels in RC vinegar-treated groups was found similar to ALEN, but differed significantly from that in sham group. The results highlight the prophylactic and curative potential of dietary vinegar against postmenopausal osteoporosis. RC vinegar could be an effective natural alternative for the prevention of postmenopausal osteoporosis. Full article
(This article belongs to the Section Metabolites)
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Open AccessCommunication Imidazole Alkaloids from the South China Sea Sponge Pericharax heteroraphis and Their Cytotoxic and Antiviral Activities
Molecules 2016, 21(2), 150; doi:10.3390/molecules21020150
Received: 25 November 2015 / Revised: 19 January 2016 / Accepted: 21 January 2016 / Published: 26 January 2016
Cited by 2 | PDF Full-text (954 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Marine sponges continue to serve as a rich source of alkaloids possessing interesting biological activities and often exhibiting unique structural frameworks. In the current study, chemical investigation on the marine sponge Pericharax heteroraphis collected from the South China Sea yielded one new imidazole
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Marine sponges continue to serve as a rich source of alkaloids possessing interesting biological activities and often exhibiting unique structural frameworks. In the current study, chemical investigation on the marine sponge Pericharax heteroraphis collected from the South China Sea yielded one new imidazole alkaloid named naamidine J (1) along with four known ones (25). Their structures were established by extensive spectroscopic methods and comparison of their data with those of the related known compounds. All the isolates possessed a central 2-aminoimidazole ring, substituted by one or two functionalized benzyl groups in some combination of the C4 and C5 positions. The cytotoxicities against selected HL-60, HeLa, A549 and K562 tumor cell lines and anti-H1N1 (Influenza a virus (IAV)) activity for the isolates were evaluated. Compounds 1 and 2 exhibited cytotoxicities against the K562 cell line with IC50 values of 11.3 and 9.4 μM, respectively. Compound 5 exhibited weak anti-H1N1 (influenza a virus, IAV) activity with an inhibition ratio of 33%. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Design of a MCoTI-Based Cyclotide with Angiotensin (1-7)-Like Activity
Molecules 2016, 21(2), 152; doi:10.3390/molecules21020152
Received: 28 December 2015 / Revised: 20 January 2016 / Accepted: 22 January 2016 / Published: 26 January 2016
Cited by 8 | PDF Full-text (2826 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using
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We report for the first time the design and synthesis of a novel cyclotide able to activate the unique receptor of angiotensin (1-7) (AT1-7), the MAS1 receptor. This was accomplished by grafting an AT1-7 peptide analog onto loop 6 of cyclotide MCoTI-I using isopeptide bonds to preserve the α-amino and C-terminal carboxylate groups of AT1-7, which are required for activity. The resulting cyclotide construct was able to adopt a cyclotide-like conformation and showed similar activity to that of AT1-7. This cyclotide also showed high stability in human serum thereby providing a promising lead compound for the design of a novel type of peptide-based in the treatment of cancer and myocardial infarction. Full article
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Open AccessArticle Binding between Saikosaponin C and Human Serum Albumin by Fluorescence Spectroscopy and Molecular Docking
Molecules 2016, 21(2), 153; doi:10.3390/molecules21020153
Received: 11 November 2015 / Revised: 18 January 2016 / Accepted: 21 January 2016 / Published: 28 January 2016
Cited by 6 | PDF Full-text (5430 KB) | HTML Full-text | XML Full-text
Abstract
Saikosaponin C (SSC) is one of the major active constituents of dried Radix bupleuri root (Chaihu in Chinese) that has been widely used in China to treat a variety of conditions, such as liver disease, for many centuries. The binding of SSC to
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Saikosaponin C (SSC) is one of the major active constituents of dried Radix bupleuri root (Chaihu in Chinese) that has been widely used in China to treat a variety of conditions, such as liver disease, for many centuries. The binding of SSC to human serum albumin (HSA) was explored by fluorescence, circular dichroism (CD), UV-vis spectrophotometry, and molecular docking to understand both the pharmacology and the basis of the clinical use of SSC/Chaihu. SSC produced a concentration-dependent quenching effect on the intrinsic fluorescence of HSA, accompanied by a blue shift in the fluorescence spectra. The Stern-Volmer equation showed that this quenching was dominated by static quenching. The binding constant of SSC with HSA was 3.72 × 103 and 2.99 × 103 L·mol−1 at 26 °C and 36 °C, respectively, with a single binding site on each SSC and HSA molecule. Site competitive experiments demonstrated that SSC bound to site I (subdomain IIA) and site II (subdomain IIIA) in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for SSC-HSA association. The energy transfer efficiency and binding distance between SSC and HSA was calculated to be 0.23 J and 2.61 nm at 26 °C, respectively. Synchronous fluorescence and CD measurements indicated that SSC affected HSA conformation in the SSC-HSA complex. Molecular docking supported the experimental findings in conformational changes, binding sites and binding forces, and revealed binding of SSC at the interface between subdomains IIA-IIB. Full article
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Open AccessArticle Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds
Molecules 2016, 21(2), 155; doi:10.3390/molecules21020155
Received: 15 December 2015 / Revised: 15 January 2016 / Accepted: 22 January 2016 / Published: 29 January 2016
PDF Full-text (1865 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A (pyridazinyl)acetate derivative was reacted with thiosemicarbazide and hydrazine hydrate to yield spiropyridazinone and acetohydrazide derivatives, respectively. The acetohydrazide derivative was used as a starting material for synthesizing some new heterocyclic compounds such as oxoindolinylidene, dimethylpyrazolyl, methylpyrazolyl, oxopyrazolyl, cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives. The
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A (pyridazinyl)acetate derivative was reacted with thiosemicarbazide and hydrazine hydrate to yield spiropyridazinone and acetohydrazide derivatives, respectively. The acetohydrazide derivative was used as a starting material for synthesizing some new heterocyclic compounds such as oxoindolinylidene, dimethylpyrazolyl, methylpyrazolyl, oxopyrazolyl, cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives. The behavior of the cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives towards nitrogen and carbon nucleophiles was investigated. The assigned structures of the prepared compounds were elucidated by spectral methods (IR, 1H-NMR 13C-NMR and mass spectroscopy). Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines, namely hepatocellular carcinoma (liver) HePG-2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis, Structure and Cytotoxic Activity of Mono- and Dialkoxy Derivatives of 5,8-Quinolinedione
Molecules 2016, 21(2), 156; doi:10.3390/molecules21020156
Received: 20 November 2015 / Revised: 7 December 2015 / Accepted: 11 December 2015 / Published: 27 January 2016
Cited by 4 | PDF Full-text (5648 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of 5,8-quinolinedione derivatives containing one or two alkoxy groups was synthesized and characterized by 1H- and 13C-NMR, IR and MS spectra. X-ray diffraction was used to investigate the crystal structures of 6-chloro-7-(2-cyjanoethoxy)-5,8-quinolinedione and 6,7-di(2,2,2-trifloroethoxy)-5,8-quinolinedione. All studied compounds were tested
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A series of 5,8-quinolinedione derivatives containing one or two alkoxy groups was synthesized and characterized by 1H- and 13C-NMR, IR and MS spectra. X-ray diffraction was used to investigate the crystal structures of 6-chloro-7-(2-cyjanoethoxy)-5,8-quinolinedione and 6,7-di(2,2,2-trifloroethoxy)-5,8-quinolinedione. All studied compounds were tested in vitro for their antiproliferative activity against three human cancer cell lines and human normal fibroblasts. Most of the compounds showed higher cytotoxicity than the starting compound, 6,7-dichloro-5,8-quinolinedione, and cisplatin, which was used as a reference agent. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus)
Molecules 2016, 21(2), 157; doi:10.3390/molecules21020157
Received: 8 December 2015 / Revised: 7 January 2016 / Accepted: 21 January 2016 / Published: 28 January 2016
Cited by 3 | PDF Full-text (2463 KB) | HTML Full-text | XML Full-text
Abstract
A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based metabolite
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A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based metabolite profiling. Total phenolics and flavonoids and their in vitro antioxidant activities were assessed. Pelargonidins were found to be the major anthocyanin in the cultivars studied. The cultivar Man Tang Hong showed the highest level of anthocyanins (1.89 ± 0.07 mg/g), phenolics (0.0664 ± 0.0033 mg/g) and flavonoids (0.0096 ± 0.0004 mg/g). Here; the variation of secondary metabolites in the radishes is described, as well as their association with primary metabolites. The low-molecular-weight hydrophilic metabolite profiles were subjected to principal component analysis (PCA), hierarchical clustering analysis (HCA), Pearson’s correlation analysis. PCA fully distinguished the three radish cultivars tested. The polar metabolites were strongly correlated between metabolites that participate in the TCA cycle. The chemometrics results revealed that TCA cycle intermediates and free phenolic acids as well as anthocyanins were higher in the cultivar Man Tang Hong than in the others. Furthermore; superoxide radical scavenging activities and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging were investigated to elucidate the antioxidant activity of secondary metabolites in the cultivars. Man Tang Hong showed the highest superoxide radical scavenging activity (68.87%) at 1000 μg/mL, and DPPH activity (20.78%), followed by Seo Ho and then Hong Feng No. 1. The results demonstrate that GC-TOFMS-based metabolite profiling, integrated with chemometrics, is an applicable method for distinguishing phenotypic variation and determining biochemical reactions connecting primary and secondary metabolism. Therefore; this study might provide information on the relationship between primary and secondary metabolites and a synergistic antioxidant ability derived from the secondary metabolites in the radish cultivars. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Design and Characterization of a Novel p1025 Peptide-Loaded Liquid Crystalline System for the Treatment of Dental Caries
Molecules 2016, 21(2), 158; doi:10.3390/molecules21020158
Received: 18 November 2015 / Revised: 19 January 2016 / Accepted: 25 January 2016 / Published: 28 January 2016
Cited by 4 | PDF Full-text (1191 KB) | HTML Full-text | XML Full-text
Abstract
Dental caries, mainly caused by the adhesion of Streptococcus mutans to pellicle-coated tooth surfaces, is an important public health problem worldwide. A synthetic peptide (p1025) corresponding to residues 1025–1044 of the adhesin can inhibit this binding. Peptides are particularly susceptible to the biological
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Dental caries, mainly caused by the adhesion of Streptococcus mutans to pellicle-coated tooth surfaces, is an important public health problem worldwide. A synthetic peptide (p1025) corresponding to residues 1025–1044 of the adhesin can inhibit this binding. Peptides are particularly susceptible to the biological environment; therefore, a p1025 peptide-loaded liquid crystalline system (LCS) consisting of tea tree oil as the oil phase, polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol as the surfactant, and water or 0.5% polycarbophil polymer dispersions as the aqueous phase was employed as a drug delivery platform. This system exhibited anticaries and bioadhesive properties and provided a protective environment to p1025 at the site of action, thereby modulating its action, prolonging its contact with the teeth, and decreasing the frequency of administration. LCSs were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and rheological, texture, and bioadhesive tests. PLM and SAXS revealed the presence of hexagonal liquid crystalline phases and microemulsions. Rheological analyses demonstrated that the addition of polymer dispersions favored characteristics such as shear thinning and thixotropy, hence improving buccal application. Bioadhesion tests showed that polymer dispersions contributed to the adhesion onto the teeth. Taken together, LCS could provide a novel pharmaceutical nanotechnology platform for dental caries treatment. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Naphthalenones and Depsidones from a Sponge-Derived Strain of the Fungus Corynespora cassiicola
Molecules 2016, 21(2), 160; doi:10.3390/molecules21020160
Received: 15 December 2015 / Revised: 23 January 2016 / Accepted: 26 January 2016 / Published: 28 January 2016
Cited by 2 | PDF Full-text (457 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new naphthalenones, corynenones A and B (1 and 2), and one new depsidone, corynesidone E (3), together with one known depsidone, corynesidone A (4) and two known diphenyl ethers, corynethers A (5) and B
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Two new naphthalenones, corynenones A and B (1 and 2), and one new depsidone, corynesidone E (3), together with one known depsidone, corynesidone A (4) and two known diphenyl ethers, corynethers A (5) and B (6), were isolated from the sponge-derived fungus Corynespora cassiicola XS-20090I7. Their structures including absolute configurations were determined by spectroscopic data and electronic circular dichroism (ECD) spectra. Compounds 4 and 5 showed cytotoxicity against human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cell lines. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Acetaminophen Induced Hepatotoxicity in Wistar Rats—A Proteomic Approach
Molecules 2016, 21(2), 161; doi:10.3390/molecules21020161
Received: 19 November 2015 / Revised: 31 December 2015 / Accepted: 22 January 2016 / Published: 28 January 2016
Cited by 5 | PDF Full-text (4983 KB) | HTML Full-text | XML Full-text
Abstract
Understanding the mechanism of chemical toxicity, which is essential for cross-species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the
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Understanding the mechanism of chemical toxicity, which is essential for cross-species and dose extrapolations, is a major challenge for toxicologists. Standard mechanistic studies in animals for examining the toxic and pathological changes associated with the chemical exposure have often been limited to the single end point or pathways. Toxicoproteomics represents a potential aid to the toxicologist to understand the multiple pathways involved in the mechanism of toxicity and also determine the biomarkers that are possible to predictive the toxicological response. We performed an acute toxicity study in Wistar rats with the prototype liver toxin; the acetaminophen (APAP) effects on protein profiles in the liver and its correlation with the plasma biochemical markers for liver injury were analyzed. Three separate groups—control, nontoxic (150 mg/kg) and toxic dose (1500 mg/kg) of APAP—were studied. The proteins extracted from the liver were separated by 2-DE and analyzed by MALDI-TOF. The differential proteins in the gels were analyzed by BIORAD’s PDQuest software and identified by feeding the peptide mass fingerprint data to various public domain programs like Mascot and MS-Fit. The identified proteins in toxicity-induced rats were classified based on their putative protein functions, which are oxidative stress (31%), immunity (14%), neurological related (12%) and transporter proteins (2%), whereas in non-toxic dose-induced rats they were oxidative stress (9%), immunity (6%), neurological (14%) and transporter proteins (9%). It is evident that the percentages of oxidative stress and immunity-related proteins were up-regulated in toxicity-induced rats as compared with nontoxic and control rats. Some of the liver drug metabolizing and detoxifying enzymes were depleted under toxic conditions compared with non-toxic rats. Several other proteins were identified as a first step in developing an in-house rodent liver toxicoproteomics database. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Regulation of Candida albicans Interaction with Macrophages through the Activation of HOG Pathway by Genistein
Molecules 2016, 21(2), 162; doi:10.3390/molecules21020162
Received: 13 December 2015 / Revised: 18 January 2016 / Accepted: 25 January 2016 / Published: 28 January 2016
Cited by 2 | PDF Full-text (1073 KB) | HTML Full-text | XML Full-text
Abstract
The severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects
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The severity of infections caused by Candida albicans, the most common opportunistic human fungal pathogen, needs rapid and effective antifungal treatments. One of the effective ways is to control the virulence factors of the pathogen. Therefore, the current study examined the effects of genistein, a natural isoflavone present in soybeans, on C. albicans. The genistein-treated C. albicans cells were then exposed to macrophages. Although no inhibition effect on the growth rates of C. albicans was noted an enhancement of the immune response to macrophages has been observed, indicated by phagocytosis and release of cytokines TNF-α and IL-10. The effect of genistein on the enhanced phagocytosis can be mimicked by the fungicides fludioxonil or iprodione, which inhibit the histidine kinase Cos1p and lead to activation of HOG pathway. The western blot results showed a clear phosphorylation of Hog1p in the wild type strain of C. albicans after incubation with genistein. In addition, effects of genistein on the phosphorylation of Hog1p in the histidine kinase mutants Δcos1 and Δsln1 were also observed. Our results thus indicate a new bio-activity of genistein on C. albicans by activation of the HOG pathway of the human pathogen C. albicans. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle A Sustainable Approach to the Stereoselective Synthesis of Diazaheptacyclic Cage Systems Based on a Multicomponent Strategy in an Ionic Liquid
Molecules 2016, 21(2), 165; doi:10.3390/molecules21020165
Received: 14 December 2015 / Revised: 21 January 2016 / Accepted: 26 January 2016 / Published: 29 January 2016
PDF Full-text (1737 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The microwave-assisted three-component reactions of 3,5-bis(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic α-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
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Open AccessArticle Insight of Saffron Proteome by Gel-Electrophoresis
Molecules 2016, 21(2), 167; doi:10.3390/molecules21020167
Received: 16 December 2015 / Revised: 22 January 2016 / Accepted: 26 January 2016 / Published: 29 January 2016
Cited by 4 | PDF Full-text (2627 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Saffron is a spice comprised of the dried stigmas and styles of Crocus sativus L. flowers and, since it is very expensive, it is frequently adulterated. So far, proteomic tools have never been applied to characterize the proteome of saffron or identify possible
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Saffron is a spice comprised of the dried stigmas and styles of Crocus sativus L. flowers and, since it is very expensive, it is frequently adulterated. So far, proteomic tools have never been applied to characterize the proteome of saffron or identify possible cases of fraud. In this study, 1D-Gel Electrophoresis was carried out to characterize the protein profile of (i) fresh stigmas and styles of the plant; (ii) dried stigmas and styles from different geographical origins (Spanish, Italian, Greek and Iranian) that had been stored for various periods of time after their processing; and (iii) two common plant adulterants, dried petals of Carthamus tinctorius L. and dried fruits of Gardenia jasminoides Ellis. A selective protein extraction protocol was applied to avoid interference from colored saffron metabolites, such as crocins, during electrophoretic analyses of saffron. We succeeded in separating and assigning the molecular weights to more than 20 proteins. In spite of the unavailability of the genome of saffron, we were able to identify five proteins by Peptide Mass Fingerprinting: phosphoenolpyruvate carboxylase 3, heat shock cognate 70 KDa protein, crocetin glucosyltransferase 2, α-1,4-glucan-protein synthase and glyceraldehydes-3-phosphate dehydrogenase-2. Our findings indicate that (i) few bands are present in all saffron samples independently of origin and storage time, with amounts that significantly vary among samples and (ii) aging during saffron storage is associated with a reduction in the number of detectable bands, suggesting that proteases are still active. The protein pattern of saffron was quite distinct from those of two common adulterants, such as the dried petals of Carthamus tinctorius and the dried fruits of Gardenia jasminoides indicating that proteomic analyses could be exploited for detecting possible frauds. Full article
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Open AccessArticle Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells
Molecules 2016, 21(2), 168; doi:10.3390/molecules21020168
Received: 9 December 2015 / Revised: 13 January 2016 / Accepted: 20 January 2016 / Published: 29 January 2016
Cited by 5 | PDF Full-text (2003 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE) on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs) and macrophages was
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Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE) on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs) and macrophages was investigated. Its effect on endothelial dysfunction (ED) was analyzed in human umbilical vein endothelial cells (HUVECs). Murine macrophages (RAW264.7 cells), PBLs and HUVECs were incubated with TAE. They were activated with LPS or TNF-α in order to induce inflammatory processes and ED, respectively. Inflammatory mediators and adhesion molecules were measured by immune assay-based multiplex analysis. Gene expression was quantified by RT-PCR. TAE altered the production of interleukins (IL-1β, IL-6, IL-10, IL-12) and chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CXCL8/IL-8, CXCL10/IP-10) in PBLs. TAE reduced ED-associated expression of adhesion molecules (ICAM-1, VCAM-1) in endothelial cell. In macrophages, the production of nitric oxide, PGE2, cytokines and ILs (TNF-α, IL-1β, IL-6, IL-12), which reflects chronic inflammatory processes, was reduced. Adenosine was identified as the main bioactive of TAE. Thus, TAE had cell-specific and context-dependent effects. We infer from these in vitro data, that during acute inflammation TAE enhances cellular alertness and therefore the sensing of disturbed immune homeostasis in the vascular-endothelial compartment. Conversely, it blunts inflammatory mediators in macrophages during chronic inflammation. A novel concept of immune regulation by this extract is proposed. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
Open AccessArticle Synthesis of the Fatty Esters of Solketal and Glycerol-Formal: Biobased Specialty Chemicals
Molecules 2016, 21(2), 170; doi:10.3390/molecules21020170
Received: 22 December 2015 / Revised: 22 January 2016 / Accepted: 25 January 2016 / Published: 30 January 2016
Cited by 3 | PDF Full-text (1012 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The caprylic, lauric, palmitic and stearic esters of solketal and glycerol formal were synthesized with high selectivity and in good yields by a solvent-free acid catalyzed procedure. No acetal hydrolysis was observed, notwithstanding the acidic reaction conditions. Full article
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Open AccessArticle Synthesis and Characterization of Macrocyclic Polyether N,N′-Diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6
Molecules 2016, 21(2), 171; doi:10.3390/molecules21020171
Received: 14 December 2015 / Revised: 25 January 2016 / Accepted: 27 January 2016 / Published: 29 January 2016
Cited by 1 | PDF Full-text (1677 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study an efficient and direct production procedure for a macrocyclic polyether N,N′-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethyl)prop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium
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In this study an efficient and direct production procedure for a macrocyclic polyether N,N′-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethyl)prop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium hydroxide to enhance the cyclization process, and at the end of the reaction, the reaction mixture is neutralized and the solvent replaced with water in-situ through distillation to afford a relatively pure precipitate that is easily recrystallized from acetone. The yield of the macrocycle was 36%–45% and could be scaled-up to one-mole quantities. The structure and purity of this compound was verified on the basis of elemental analysis, IR, UV-Vis, 1H-, 13C-NMR, 2D-NMR, mass spectroscopy, and thermal analysis. The white crystalline compound has a sharp melting point of 124 °C and a crystallization temperature of 81.4 °C determined by differential scanning calorimetry. Our motivation behind the synthesis of the bibracchial lariat azacrown polyether ligand was to examine its possible applications in ion-selective polymer-supported materials. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Synthesis and Characterization of Novel Polythiophenes Containing Pyrene Chromophores: Thermal, Optical and Electrochemical Properties
Molecules 2016, 21(2), 172; doi:10.3390/molecules21020172
Received: 14 December 2015 / Revised: 22 January 2016 / Accepted: 25 January 2016 / Published: 30 January 2016
Cited by 4 | PDF Full-text (4320 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of pyrene containing thiophene monomers TPM15 were synthesized and fully characterized by FTIR, MS, 1H- and 13C-NMR spectroscopy; their thermal properties were determined by TGA and DSC. These monomers were chemically polymerized using FeCl3 as
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A novel series of pyrene containing thiophene monomers TPM15 were synthesized and fully characterized by FTIR, MS, 1H- and 13C-NMR spectroscopy; their thermal properties were determined by TGA and DSC. These monomers were chemically polymerized using FeCl3 as oxidizing agent to give the corresponding oligomers TPO15) and they were electrochemically polymerized to obtain the corresponding polymer films deposited onto ITO. All oligomers exhibited good thermal stability, with T10 values between 255 and 299 °C, and Tg values varying from 36 to 39 °C. The monomers showed an absorption band at 345 nm due to the S0 → S2 transition of the pyrene group, whereas the fluorescence spectra showed a broad emission band arising from the “monomer” emission at 375–420 nm. The obtained polymers exhibited two absorption bands at 244 and 354 nm, due to the polythiophene and the pyrene moieties, respectively. The fluorescence spectra of polymers showed a broad “monomer” emission at 380–420 nm followed by an intense excimer emission band at 570 nm, due to the presence of intramolecular pyrene-pyrene interactions in these compounds. Full article
(This article belongs to the Special Issue Photoactive Molecules)
Open AccessArticle Inhibitory Effect of Rosa rugosa Tea Extract on the Formation of Heterocyclic Amines in Meat Patties at Different Temperatures
Molecules 2016, 21(2), 173; doi:10.3390/molecules21020173
Received: 5 November 2015 / Revised: 17 January 2016 / Accepted: 22 January 2016 / Published: 30 January 2016
Cited by 4 | PDF Full-text (2792 KB) | HTML Full-text | XML Full-text
Abstract
In previous studies, heterocyclic amines (HCAs) have been identified as carcinogenic and a risk factor for human cancer. Therefore, the present study was designed to identify bioactive natural products capable of controlling the formation of HCAs during cooking. For this purpose we have
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In previous studies, heterocyclic amines (HCAs) have been identified as carcinogenic and a risk factor for human cancer. Therefore, the present study was designed to identify bioactive natural products capable of controlling the formation of HCAs during cooking. For this purpose we have evaluated the effect of Rosa rugosa tea extract (RTE) on the formation of HCAs in ground beef patties fried at 160 °C or 220 °C. RTE is rich in phenolic compounds and capable of inhibiting the formation of free radicals. The pyrido[3,4-b]indole (norharman) and 1-methyl-9H-pyrido[3,4-b]indole (harman) contents were significantly (p < 0.05) decreased in RTE-treated patties at 220 °C. 9H-3-Amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) and 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole acetate (Trp-P-1) were not detected at 160 °C and were statistically (p < 0.01) reduced at 220 °C compared to the control. RTE remarkably inhibited the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) at 220 °C (p < 0.001) and at 160 °C (p < 0.05). 2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-3-methyl-9H-pyrido[2,3-b]-indole (MeAαC) were only detected in the control group at 160 °C but were comparatively (p > 0.05) similar in the control and treated groups at 220 °C. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline (4,8-DiMeIQx) were not detected in any sample. Total HCAs were positively correlated with cooking loss. In the RTE-treated groups, 75% of the total HCAs were decreased at 160 °C and 46% at 220 °C, suggesting that RTE is effective at both temperatures and can be used during cooking at high temperatures to lessen the amount of HCAs formed. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antioxidant and DNA Damage Protecting Activity of Exopolysaccharides from the Endophytic Bacterium Bacillus cereus SZ1
Molecules 2016, 21(2), 174; doi:10.3390/molecules21020174
Received: 25 December 2015 / Revised: 25 January 2016 / Accepted: 27 January 2016 / Published: 4 February 2016
Cited by 7 | PDF Full-text (2506 KB) | HTML Full-text | XML Full-text
Abstract
An endophytic bacterium was isolated from the Chinese medicinal plant Artemisia annua L. The phylogenetic and physiological characterization indicated that the isolate, strain SZ-1, was Bacillus cereus. The endophyte could produce an exopolysaccharide (EPS) at 46 mg/L. The 1,1-diphenyl-2-picrylhydracyl (DPPH) radical scavenging
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An endophytic bacterium was isolated from the Chinese medicinal plant Artemisia annua L. The phylogenetic and physiological characterization indicated that the isolate, strain SZ-1, was Bacillus cereus. The endophyte could produce an exopolysaccharide (EPS) at 46 mg/L. The 1,1-diphenyl-2-picrylhydracyl (DPPH) radical scavenging activity of the EPS reached more than 50% at 3–5 mg/mL. The EPS was also effective in scavenging superoxide radical in a concentration dependent fashion with an EC50 value of 2.6 mg/mL. The corresponding EC50 for scavenging hydroxyl radical was 3.1 mg/mL. Moreover, phenanthroline-copper complex-mediated chemiluminescent emission of DNA damage was both inhibited and delayed by EPS. The EPS at 0.7–1.7 mg/mL also protected supercoiled DNA strands in plasmid pBR322 against scission induced by Fenton-mediated hydroxyl radical. The preincubation of PC12 cells with the EPS prior to H2O2 exposure increased the cell survival and glutathione (GSH) level and catalase (CAT) activities, and decreased the level of malondialdehyde (MDA) and lactate dehydrogenase (LDH) activity in a dose-dependent manner, suggesting a pronounced protective effect against H2O2-induced cytotoxicity. Our study indicated that the EPS could be useful for preventing oxidative DNA damage and cellular oxidation in pharmaceutical and food industries. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Self Organizing Map-Based Classification of Cathepsin k and S Inhibitors with Different Selectivity Profiles Using Different Structural Molecular Fingerprints: Design and Application for Discovery of Novel Hits
Molecules 2016, 21(2), 175; doi:10.3390/molecules21020175
Received: 21 December 2015 / Revised: 20 January 2016 / Accepted: 27 January 2016 / Published: 30 January 2016
Cited by 1 | PDF Full-text (4015 KB) | HTML Full-text | XML Full-text
Abstract
The main step in a successful drug discovery pipeline is the identification of small potent compounds that selectively bind to the target of interest with high affinity. However, there is still a shortage of efficient and accurate computational methods with powerful capability to
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The main step in a successful drug discovery pipeline is the identification of small potent compounds that selectively bind to the target of interest with high affinity. However, there is still a shortage of efficient and accurate computational methods with powerful capability to study and hence predict compound selectivity properties. In this work, we propose an affordable machine learning method to perform compound selectivity classification and prediction. For this purpose, we have collected compounds with reported activity and built a selectivity database formed of 153 cathepsin K and S inhibitors that are considered of medicinal interest. This database has three compound sets, two K/S and S/K selective ones and one non-selective KS one. We have subjected this database to the selectivity classification tool ‘Emergent Self-Organizing Maps’ for exploring its capability to differentiate selective cathepsin inhibitors for one target over the other. The method exhibited good clustering performance for selective ligands with high accuracy (up to 100 %). Among the possibilites, BAPs and MACCS molecular structural fingerprints were used for such a classification. The results exhibited the ability of the method for structure-selectivity relationship interpretation and selectivity markers were identified for the design of further novel inhibitors with high activity and target selectivity. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessArticle Metabolites of Siamenoside I and Their Distributions in Rats
Molecules 2016, 21(2), 176; doi:10.3390/molecules21020176
Received: 3 January 2016 / Revised: 25 January 2016 / Accepted: 27 January 2016 / Published: 30 January 2016
Cited by 2 | PDF Full-text (884 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic
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Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Moving from Classical Ru-NHC to Neutral or Charged Rh-NHC Based Catalysts in Olefin Metathesis
Molecules 2016, 21(2), 177; doi:10.3390/molecules21020177
Received: 23 December 2015 / Revised: 13 January 2016 / Accepted: 28 January 2016 / Published: 30 January 2016
Cited by 5 | PDF Full-text (737 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Considering the versatility of oxidation states of rhodium together with the successful background of ruthenium-N-heterocyclic carbene based catalysts in olefin metathesis, it is envisaged the exchange of the ruthenium of the latter catalysts by rhodium, bearing an open-shell neutral rhodium center,
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Considering the versatility of oxidation states of rhodium together with the successful background of ruthenium-N-heterocyclic carbene based catalysts in olefin metathesis, it is envisaged the exchange of the ruthenium of the latter catalysts by rhodium, bearing an open-shell neutral rhodium center, or a +1 charged one. In the framework of in silico experiments, density functional theory (DFT) calculations have been used to plot the first catalytic cycle that as a first step includes the release of the phosphine. DFT is, in this case, the tool that allows the discovery of the less endergonic reaction profile from the precatalytic species for the neutral catalyst with respect to the corresponding ruthenium one; increasing the endergonic character when dealing with the charged system. Full article
(This article belongs to the Special Issue Olefin Metathesis)
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Open AccessArticle Unusual Nitrogenous Phenalenone Derivatives from the Marine-Derived Fungus Coniothyrium cereale
Molecules 2016, 21(2), 178; doi:10.3390/molecules21020178
Received: 30 December 2015 / Revised: 26 January 2016 / Accepted: 27 January 2016 / Published: 1 February 2016
Cited by 1 | PDF Full-text (2211 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The new phenalenone metabolites 1, 2, 4, and 6 were isolated from the marine-derived endophytic fungus Coniothyrium cereale, in addition to the ergostane-type sterol (3) and entatrovenetinone (5). Compounds 1 and 2 represent two unusual
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The new phenalenone metabolites 1, 2, 4, and 6 were isolated from the marine-derived endophytic fungus Coniothyrium cereale, in addition to the ergostane-type sterol (3) and entatrovenetinone (5). Compounds 1 and 2 represent two unusual nitrogen-containing compounds, which are composed of a sterol portion condensed via two bonds to phenalenone derivatives. Compound 6, which contains unprecedented imine functionality between two carbonyl groups to form a oxepane -imine-dione ring, exhibited a moderate cytotoxicity against K562, U266, and SKM1 cancer cell lines. Moreover, molecular docking studies were done on estrogen receptor α-ligand binding domain (ERα-LBD) to compounds 1 and 2 to correlate with binding energies and affinities calculated from molecular docking to the anti-proliferative activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Thiourea-Modified TiO2 Nanorods with Enhanced Photocatalytic Activity
Molecules 2016, 21(2), 181; doi:10.3390/molecules21020181
Received: 5 December 2015 / Revised: 24 January 2016 / Accepted: 28 January 2016 / Published: 1 February 2016
Cited by 5 | PDF Full-text (4271 KB) | HTML Full-text | XML Full-text
Abstract
Semiconductor TiO2 photocatalysis has attracted much attention due to its potential application in solving the problems of environmental pollution. In this paper, thiourea (CH4N2S) modified anatase TiO2 nanorods were fabricated by calcination of the mixture of TiO
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Semiconductor TiO2 photocatalysis has attracted much attention due to its potential application in solving the problems of environmental pollution. In this paper, thiourea (CH4N2S) modified anatase TiO2 nanorods were fabricated by calcination of the mixture of TiO2 nanorods and thiourea at 600 °C for 2 h. It was found that only N element was doped into the lattice of TiO2 nanorods. With increasing the weight ratio of thiourea to TiO2 (R) from 0 to 8, the light-harvesting ability of the photocatalyst steady increases. Both the crystallization and photocatalytic activity of TiO2 nanorods increase first and then decrease with increase in R value, and R2 sample showed the highest crystallization and photocatalytic activity in degradation of Brilliant Red X3B (X3B) and Rhodamine B (RhB) dyes under visible light irradiation (λ > 420 nm). The increased visible-light photocatalytic activity of the prepared N-doped TiO2 nanorods is due to the synergistic effects of the enhanced crystallization, improved light-harvesting ability and reduced recombination rate of photo-generated electron-hole pairs. Note that the enhanced visible photocatalytic activity of N-doped nanorods is not based on the scarification of their UV photocatalytic activity. Full article
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Open AccessArticle Alisol F 24 Acetate Enhances Chemosensitivity and Apoptosis of MCF-7/DOX Cells by Inhibiting P-Glycoprotein-Mediated Drug Efflux
Molecules 2016, 21(2), 183; doi:10.3390/molecules21020183
Received: 30 November 2015 / Revised: 26 January 2016 / Accepted: 28 January 2016 / Published: 4 February 2016
Cited by 4 | PDF Full-text (3020 KB) | HTML Full-text | XML Full-text
Abstract
Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast cancer cell line. We found that ALI was
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Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast cancer cell line. We found that ALI was a potent P-glycoprotein (P-gp) inhibitor, in the Caco-2-monolayer cell model. ALI showed a significant and concentration-dependent cytotoxic effect on MCF-7/DOX cells in combination with doxorubicin by increasing intracellular accumulation and inducing nuclear migration of doxorubicin. However, ALI had no such effect on MCF-7 cells. In addition, ALI also promoted doxorubicin-induced early apoptosis of MCF-7/DOX cells in a time-dependent manner. These results suggest that ALI can enhance chemosensitivity of doxorubicin and reinforce its anti-cancer effect by increasing its uptake, especially inducing its nuclear accumulation in MCF-7/DOX cells. Therefore, ALI could be developed as a potential MDR-reversing agent in cancer chemotherapy in further study. Full article
(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)
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Open AccessArticle Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors
Molecules 2016, 21(2), 185; doi:10.3390/molecules21020185
Received: 11 January 2016 / Revised: 27 January 2016 / Accepted: 27 January 2016 / Published: 4 February 2016
Cited by 1 | PDF Full-text (1271 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The geometries and energies of factor Xa inhibitors edoxaban, eribaxaban, fidexaban, darexaban, letaxaban, and the dual factor Xa and thrombin inhibitors tanogitran and SAR107375 in both the gas-phase and aqueous solution were studied using the Becke3LYP/6-31++G(d,p) or Grimme’s B97D/6-31++G(d,p) method. The fully optimized
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The geometries and energies of factor Xa inhibitors edoxaban, eribaxaban, fidexaban, darexaban, letaxaban, and the dual factor Xa and thrombin inhibitors tanogitran and SAR107375 in both the gas-phase and aqueous solution were studied using the Becke3LYP/6-31++G(d,p) or Grimme’s B97D/6-31++G(d,p) method. The fully optimized conformers of these anticoagulants show a characteristic l-shape structure, and the water had a remarkable effect on the equilibrium geometry. According to the calculated pKa values eribaxaban and letaxaban are in neutral undissociated form at pH 7.4, while fidexaban and tanogitran exist as zwitterionic structures. The lipophilicity of the inhibitors studied lies within a large range of log P between 1 and 4. The dual inhibitor SAR107375 represents an improvement in structural, physicochemical and pharmacokinetic characteristics over tanogitran. At blood pH, SAR107375 predominantly exists in neutral form. In contrast with tanogitran, it is better absorbed and more lipophilic and active after oral application. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Peltomexicanin, a Peltogynoid Quinone Methide from Peltogyne Mexicana Martínez Purple Heartwood
Molecules 2016, 21(2), 186; doi:10.3390/molecules21020186
Received: 17 November 2015 / Revised: 15 January 2016 / Accepted: 28 January 2016 / Published: 4 February 2016
PDF Full-text (360 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Peltomexicanin (7,10-dihydroxy-6,12-dioxa-5H-tetraphen-3-one) is a new peltogynoid quinone methide isolated from Palo Morado (Peltogyne mexicana Martínez) heartwood by column chromatography. Its chemical structure was elucidated by IR, NMR (1H, 13C), 2D NMR experiments (COSY, NOESY, HMQC, and HSQC),
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Peltomexicanin (7,10-dihydroxy-6,12-dioxa-5H-tetraphen-3-one) is a new peltogynoid quinone methide isolated from Palo Morado (Peltogyne mexicana Martínez) heartwood by column chromatography. Its chemical structure was elucidated by IR, NMR (1H, 13C), 2D NMR experiments (COSY, NOESY, HMQC, and HSQC), ESI-MS, and UV-Vis spectroscopic analysis. According to HPLC quantification, this compound is the main pigment and accounts for 1.21% of Palo Morado heartwood material. The antioxidant activity of peltomexicanin and dried methanolic extract (DEx) of purple heartwood was evaluated using the radical of 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and the corresponding values expressed as Trolox equivalents (µmol TE/mg sample) were 4.25 and 4.57, respectively. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle 1,3-Dipolar Cycloaddition in the Preparation of New Fused Heterocyclic Compounds via Thermal Initiation
Molecules 2016, 21(2), 187; doi:10.3390/molecules21020187
Received: 3 December 2015 / Revised: 22 January 2016 / Accepted: 29 January 2016 / Published: 4 February 2016
PDF Full-text (2242 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This paper describes the synthesis of precursors with a benzo[b]furan skeleton for the intramolecular 1,3-dipolar cycloaddition of azomethine ylides prepared from N-substituted 3-allyl-aminobenzo[b]furan-2-aldehydes and secondary amines derived from α-amino acid esters. Reactions were initiated by heating. The products
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This paper describes the synthesis of precursors with a benzo[b]furan skeleton for the intramolecular 1,3-dipolar cycloaddition of azomethine ylides prepared from N-substituted 3-allyl-aminobenzo[b]furan-2-aldehydes and secondary amines derived from α-amino acid esters. Reactions were initiated by heating. The products consisted of four fused rings with three stereogenic centers. Their structure and stereochemistry were determined by NMR spectra and X-ray measurements. Full article
(This article belongs to the Special Issue Pericyclic Reactions)
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Open AccessArticle Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake
Molecules 2016, 21(2), 188; doi:10.3390/molecules21020188
Received: 6 January 2016 / Revised: 27 January 2016 / Accepted: 1 February 2016 / Published: 4 February 2016
Cited by 2 | PDF Full-text (564 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Two new oleanane-type saponins, named oleiferasaponins C4 (1) and C5 (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-
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Two new oleanane-type saponins, named oleiferasaponins C4 (1) and C5 (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galacto-pyranosyl-(1→2)]-[β-d-glucopyranosyl-(1→2)-β-d-galactopyranosy-(1→3)]-β-d-glucopyranosid-uronic acid methyl ester (1) and 16α-hydroxy-22α-O-angeloyl-23α-aldehyde-28-dihydroxy-methylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-galactopyranosyl-(1→3)]-β-d-glucopyranosiduronic acid methyl ester (2) through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). Full article
(This article belongs to the Special Issue Triterpenes and Triterpenoids 2016)
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Open AccessArticle Design, Synthesis and Anticancer Evaluation of Novel Quinazoline-Sulfonamide Hybrids
Molecules 2016, 21(2), 189; doi:10.3390/molecules21020189
Received: 18 December 2015 / Revised: 27 January 2016 / Accepted: 29 January 2016 / Published: 4 February 2016
Cited by 8 | PDF Full-text (793 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
By combining the structural features of quinazoline and sulfonamides, novel hybrid compounds 221 were synthesized using a simple and convenient method. Evaluation of these compounds against different cell lines identified compounds 7 and 17 as most active anticancer agents as they
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By combining the structural features of quinazoline and sulfonamides, novel hybrid compounds 221 were synthesized using a simple and convenient method. Evaluation of these compounds against different cell lines identified compounds 7 and 17 as most active anticancer agents as they showed effectiveness on the four tested cell lines. The anticancer screening results of the tested compounds provides an encouraging framework that could lead to the development of potent new anticancer agents. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates
Molecules 2016, 21(2), 191; doi:10.3390/molecules21020191
Received: 5 January 2016 / Revised: 28 January 2016 / Accepted: 29 January 2016 / Published: 11 February 2016
Cited by 5 | PDF Full-text (547 KB) | HTML Full-text | XML Full-text
Abstract
Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman’s method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50
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Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman’s method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 µM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 µM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 µM). Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
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Open AccessArticle Isolation of Flavonoids from Deguelia duckeana and Their Effect on Cellular Viability, AMPK, eEF2, eIF2 and eIF4E
Molecules 2016, 21(2), 192; doi:10.3390/molecules21020192
Received: 4 November 2015 / Accepted: 29 January 2016 / Published: 6 February 2016
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Abstract
Preparations of Deguelia duckeana, known in Brazil as timbó, are used by indigenous people to kill fish. Reinvestigation of its extracts resulted in the isolation and identification of 11 known flavonoids identified as 3,5,4’-trimethoxy-4-prenylstilbene (1), 4-methoxyderricidine (2), lonchocarpine (
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Preparations of Deguelia duckeana, known in Brazil as timbó, are used by indigenous people to kill fish. Reinvestigation of its extracts resulted in the isolation and identification of 11 known flavonoids identified as 3,5,4’-trimethoxy-4-prenylstilbene (1), 4-methoxyderricidine (2), lonchocarpine (3), 4-hydroxylonchocarpine (4), 4-methoxylonchocarpine (5), 5-hydroxy-4’,7-dimethoxy-6-prenylflavanone (6), 4’-hydroxyisolonchocarpine (7), 4’-methoxyisolonchocarpine (8), 3’,4’,7-trimethoxyflavone (9), 3’,4’-methylenedioxy-7-methoxyflavone (10), and 2,2-dimethyl-chromone-5,4’-hydroxy-5’-methoxyflavone (11). Except for 1, 3, and 4 all of these flavonoids have been described for the first time in D. duckeana and the flavanone 6 for the first time in nature. Compounds 2, 3, 4, 7, 9, and 10 were studied for their potential to induce cell death in neuronal SK-N-SH cells. Only the chalcone 4 and the flavanone 7 significantly induced lactate dehydrogenase (LDH) release, which was accompanied by activation of caspase-3 and impairment of energy homeostasis in the MTT assay and may explain the killing effect on fish. Interestingly, the flavone 10 reduced cell metabolism in the MTT assay without inducing cytotoxicity in the LDH assay. Furthermore, the flavonoids 2, 3, 4, 7, and 10 induced phosphorylation of the AMP-activated protein kinase (AMPK) and the eukaryotic elongation factor 2 (eEF2). The initiation factor eIF4E was dephosphorylated in the presence of these compounds. The initiation factor eIF2alpha was not affected. Further studies are needed to elucidate the importance of the observed effects on protein synthesis and potential therapeutic perspectives. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors
Molecules 2016, 21(2), 193; doi:10.3390/molecules21020193
Received: 10 December 2015 / Revised: 30 January 2016 / Accepted: 2 February 2016 / Published: 5 February 2016
Cited by 9 | PDF Full-text (1090 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with
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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the β-amyloid (Aβ) protein, acting as a chaperone and increasing the number and neurotoxicity of Aβ fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Aβ, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole-quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
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Open AccessArticle Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide
Molecules 2016, 21(2), 194; doi:10.3390/molecules21020194
Received: 12 December 2015 / Revised: 1 February 2016 / Accepted: 2 February 2016 / Published: 5 February 2016
Cited by 2 | PDF Full-text (2002 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed “click” chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma
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A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed “click” chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC50 = 93 µM). Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate’s cytotoxicity is significantly enhanced (IC50 = 16 µM) upon brief low-power UV-A irradiation. Full article
(This article belongs to the Special Issue Photoresponsive Drugs)
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Open AccessArticle The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-κB Pathway
Molecules 2016, 21(2), 195; doi:10.3390/molecules21020195
Received: 16 January 2016 / Accepted: 26 January 2016 / Published: 5 February 2016
Cited by 7 | PDF Full-text (3465 KB) | HTML Full-text | XML Full-text
Abstract
Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in
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Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-α-induced expressions of cell adhesion molecules, chemokines and NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-α-stimulated HUVECs. The TNF-α-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-α-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-α-induced nuclear translocation of NF-κB, which resulted from the inhibited phosphorylation of IKKα/β, IκB-α and NF-κB. Altogether, we proposed that naringin modulated TNF-α-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-α-induced activation of IKK/NF-κB signaling pathway to exert the anti-atherosclerotic effect. Full article
(This article belongs to the Section Natural Products)
Open AccessFeature PaperArticle Bio-Based Solvents for Green Extraction of Lipids from Oleaginous Yeast Biomass for Sustainable Aviation Biofuel
Molecules 2016, 21(2), 196; doi:10.3390/molecules21020196
Received: 11 December 2015 / Accepted: 26 January 2016 / Published: 6 February 2016
Cited by 11 | PDF Full-text (2967 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Lipid-based oleaginous microorganisms are potential candidates and resources for the sustainable production of biofuels. This study was designed to evaluate the performance of several alternative bio-based solvents for extracting lipids from yeasts. We used experimental design and simulation with Hansen solubility simulations and
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Lipid-based oleaginous microorganisms are potential candidates and resources for the sustainable production of biofuels. This study was designed to evaluate the performance of several alternative bio-based solvents for extracting lipids from yeasts. We used experimental design and simulation with Hansen solubility simulations and the conductor-like screening model for realistic solvation (COSMO-RS) to simulate the solubilization of lipids in each of these solvents. Lipid extracts were analyzed by high performance thin-layer chromatography (HPTLC) to obtain the distribution of lipids classes and gas chromatography coupled with a flame ionization detector (GC/FID) to obtain fatty acid profiles. Our aim was to correlate simulation with experimentation for extraction and solvation of lipids with bio-based solvents in order to make a preliminary evaluation for the replacement of hexane to extract lipids from microorganisms. Differences between theory and practice were noted for several solvents, such as CPME, MeTHF and ethyl acetate, which appeared to be good candidates to replace hexane. Full article
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Open AccessArticle New Biopolymer Nanoparticles Improve the Solubility of Lipophilic Megestrol Acetate
Molecules 2016, 21(2), 197; doi:10.3390/molecules21020197
Received: 22 December 2015 / Accepted: 2 February 2016 / Published: 6 February 2016
Cited by 1 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text
Abstract
As many substances are poorly soluble in water and thus possess decreased bioavailability, creating orally administered forms of these substances is a challenge. The objective of this study was to determine whether the solubility of megestrol acetate, a Biopharmaceutical Classification System (BCS) class
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As many substances are poorly soluble in water and thus possess decreased bioavailability, creating orally administered forms of these substances is a challenge. The objective of this study was to determine whether the solubility of megestrol acetate, a Biopharmaceutical Classification System (BCS) class II drug, can be improved by using a newly-synthesized surfactant (Rofam 70: a rapeseed methyl ester ethoxylate) and compare it with two references surfactants (Tween 80, Pluronic F68) at three different pH values. Spectrophotometry was used to compare the solubility profiles in the presence of three tested surfactants at pH 5.0, 7.4 and 9.0. Rapeseed methyl ester ethoxylate was found to improve the solubility of the BCS Class II drug and increase its bioavailability; It increased drug solubility more effectively than Pluronic F68. Its cytotoxicity results indicate its possible value as a surfactant in Medicine and Pharmacy. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives
Molecules 2016, 21(2), 199; doi:10.3390/molecules21020199
Received: 7 December 2015 / Accepted: 2 February 2016 / Published: 6 February 2016
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Abstract
A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in
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A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 µM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent. Full article
Open AccessArticle The Diels-Alder Cycloaddition Reaction of Substituted Hemifullerenes with 1,3-Butadiene: Effect of Electron-Donating and Electron-Withdrawing Substituents
Molecules 2016, 21(2), 200; doi:10.3390/molecules21020200
Received: 12 December 2015 / Revised: 27 January 2016 / Accepted: 31 January 2016 / Published: 12 February 2016
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Abstract
The Diels-Alder (DA) reaction provides an attractive route to increase the number of six member rings in substituted Polycyclic Aromatic Hydrocarbons (PAHs). The density functional theory (DFT) B3LYP method has been used in this work to inquire if the substitution of H over
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The Diels-Alder (DA) reaction provides an attractive route to increase the number of six member rings in substituted Polycyclic Aromatic Hydrocarbons (PAHs). The density functional theory (DFT) B3LYP method has been used in this work to inquire if the substitution of H over the edge of triindenetriphenylene (pristine hemifullerene 1) and pentacyclopentacorannulene (pristine hemifullerene 2), could improve the DA cycloaddition reaction with 1,3-butadiene. The substituents tested include electron-donating (NH2, OMe, OH, Me, i-Pr) and electron-withdrawing groups (F, COOH, CF3, CHO, CN, NO2). The electronic, kinetic and thermodynamic parameters of the DA reactions of the substituted hemifullerenes with 1,3-butadiene have been analyzed. The most promising results were obtained for the NO2 substituent; the activation energy barriers for reactions using this substituent were lower than the barriers for the pristine hemifullerenes. This leads us to expect that the cycloadditions to a starting fullerene fragment will be possible. Full article
(This article belongs to the Special Issue Fullerene and the Related Curved-pi Materials Chemistry)
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Open AccessArticle Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability
Molecules 2016, 21(2), 201; doi:10.3390/molecules21020201
Received: 18 December 2015 / Revised: 29 January 2016 / Accepted: 1 February 2016 / Published: 8 February 2016
Cited by 5 | PDF Full-text (5415 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl)-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide
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Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl)-7-cyano-6-substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45–5.69 µM and 0.85–3.44 µM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti-inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5-carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile. Full article
(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)
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Open AccessFeature PaperArticle Design of Potent and Controllable Anticoagulants Using DNA Aptamers and Nanostructures
Molecules 2016, 21(2), 202; doi:10.3390/molecules21020202
Received: 11 December 2015 / Accepted: 3 February 2016 / Published: 6 February 2016
Cited by 4 | PDF Full-text (1423 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy
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The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy reported for these aptamers during clinical trials, multiple aptamers have been linked using DNA nanostructures. Here, we modify that strategy by linking multiple copies of various thrombin-binding aptamers using DNA weave tiles. The resulting constructs have very high anticoagulant activity in functional assays owing to their improved cooperative binding affinity to thrombin due to optimized spacing, orientation, and the high local concentration of aptamers. We also report the results of molecular dynamics simulations to gain insight into the solution conformations of the tiles. Moreover, by using DNA strand displacement, we were able to turn the coagulation cascade off and on as desired, thereby enabling significantly better control over blood coagulation. Full article
(This article belongs to the Special Issue Thrombin Inhibitors: Discovery and Design)
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Open AccessArticle Biochemical Characteristics of Three Laccase Isoforms from the Basidiomycete Pleurotus nebrodensis
Molecules 2016, 21(2), 203; doi:10.3390/molecules21020203
Received: 10 December 2015 / Accepted: 3 February 2016 / Published: 6 February 2016
Cited by 6 | PDF Full-text (1337 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The characterization of three laccase isoforms from Pleurotus nebrodensis is described. Isoenzymes Lac1, Lac2 and Lac3 were purified to homogeneity using ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose and a gel filtration step on Superdex 75. The molecular weights of the purified
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The characterization of three laccase isoforms from Pleurotus nebrodensis is described. Isoenzymes Lac1, Lac2 and Lac3 were purified to homogeneity using ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose and a gel filtration step on Superdex 75. The molecular weights of the purified laccases were estimated to be 68, 64 and 51 kDa, respectively. The isoenzymes demonstrated the same optimum pH at 3.0 but slightly different temperature optima: 50–60 °C for Lac1 and Lac3 and 60 °C for Lac2. Lac2 was always more stable than the other two isoforms and exposure to 50 °C for 120 min caused 30% loss in activity. Lac2 was relatively less stable than the other two isoforms when exposed to the pH range of 3.0–8.0 for 24 h, but inactivation only occurred initially, with around 70% residual activity being maintained during the whole process. Oxidative ability towards aromatic compounds varied substantially among the isoforms and each of them displayed preference toward some substrates. Kinetic constants (Km, Kcat) were determined by using a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assay, with Lac3 showing the best affinity and Lac2 displaying the highest catalytic efficiency. Amino acid sequences from peptides derived from digestion of isoenzymes showed great consistency with laccases in the databases. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle A Continuous Procedure Based on Column Chromatography to Purify Anthocyanins from Schisandra chinensis by a Macroporous Resin plus Gel Filtration Chromatography
Molecules 2016, 21(2), 204; doi:10.3390/molecules21020204
Received: 2 December 2015 / Accepted: 3 February 2016 / Published: 6 February 2016
Cited by 2 | PDF Full-text (2280 KB) | HTML Full-text | XML Full-text
Abstract
In our previous study, as natural food colorants and antioxidants, the color and content stabilities of Schisandra chinensis (S. chinensis) anthocyanins were investigated. In this work, the purification process parameters of S. chinensis anthocyanins using a macroporous resin and gel filtration
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In our previous study, as natural food colorants and antioxidants, the color and content stabilities of Schisandra chinensis (S. chinensis) anthocyanins were investigated. In this work, the purification process parameters of S. chinensis anthocyanins using a macroporous resin and gel filtration chromatography were evaluated. The optimized parameters of static adsorption and desorption were as follows. The selected resin is HPD-300 (nonpolar copolymer styrene type resin), and the anthocyanins adsorption saturation capacity of HPD-300 resin was 0.475 mg/g dry resin. Adsorption time was 4 h, and 0.517 mg/mL of S. chinensis anthocyanins was adsorbed on the resin column with a flow rate of 39 mL/h (3 BV/h). After adsorption, the anthocyanins were completely desorpted with 2.5 BV of 90% (v/v) ethanol solution, and the desorption flow rate was 13 mL/h (1 BV/h). After purification by dynamic adsorption and desorption, the anthocyanins content in the effluent increased from 47.6 mg/g to 128.4 mg/g, the purity of anthocyanins increased six-fold from 5.08% to 30.43%, and the anthocyanins recovery was 96.5%. The major constituent of S. chinensis anthocyanins was isolated with Bio-Gel P2 gel filtration chromatography, and it was detected by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS) as cyanidin-3-O-xylosylrutinoside. Moreover, the antioxidant activities of S. chinensis anthocyanins were investigated. After purification using the HPD-300 resin, the antioxidant activities of anthocyanins were increased 1.2-fold (FRAP) and 1.7-fold (ABTS). Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Biological Activity of Vegetal Extracts Containing Phenols on Plant Metabolism
Molecules 2016, 21(2), 205; doi:10.3390/molecules21020205
Received: 5 November 2015 / Revised: 2 February 2016 / Accepted: 3 February 2016 / Published: 8 February 2016
Cited by 7 | PDF Full-text (1096 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The influence of vegetal extracts derived from red grape, blueberry fruits and hawthorn leaves on Zea mays L. plant growth and the activity of phenylalanine ammonia-lyase (PAL), a key enzyme of the phenylpropanoid pathway, was investigated in laboratory experiments. The extracts were characterized
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The influence of vegetal extracts derived from red grape, blueberry fruits and hawthorn leaves on Zea mays L. plant growth and the activity of phenylalanine ammonia-lyase (PAL), a key enzyme of the phenylpropanoid pathway, was investigated in laboratory experiments. The extracts were characterized using FT-IR and Raman spectroscopies in order to obtain a pattern of the main functional groups. In addition, phenols content was determined by HPLC, whereas the content of indoleacetic acid and isopentenyladenosine hormones was determined by ELISA test and the auxin and gibberellin-like activities by plant-bioassays. The treated maize revealed increased root and leaf biomass, chlorophyll and sugars content with respect to untreated plants. Hawthorn, red grape skin and blueberry at 1.0 mL/L induced high p-coumaric content values, whilst hawthorn also showed high amounts of gallic and p-hydroxybenzoic acids. PAL activity induced by hawthorn at 1.0 mL/L had the highest values (11.1-fold UNT) and was strongly and linearly related with the sum of leaf phenols. Our results suggest that these vegetal extracts contain more than one group of plant-promoting substances. Full article
(This article belongs to the Section Metabolites)
Open AccessArticle Identification and Determination of the Polyhydroxylated Alkaloids Compounds with α-Glucosidase Inhibitor Activity in Mulberry Leaves of Different Origins
Molecules 2016, 21(2), 206; doi:10.3390/molecules21020206
Received: 13 January 2016 / Revised: 3 February 2016 / Accepted: 4 February 2016 / Published: 8 February 2016
Cited by 4 | PDF Full-text (1186 KB) | HTML Full-text | XML Full-text
Abstract
Mulberry leaves have commonly been utilized in China as a herbal medicine for the treatment of diabetes for thousands of years. To evaluate the quality, an ultra-high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) method was developed for
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Mulberry leaves have commonly been utilized in China as a herbal medicine for the treatment of diabetes for thousands of years. To evaluate the quality, an ultra-high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) method was developed for identification of polyhydroxylated alkaloids with α-glucosidase inhibitor activity in mulberry leaf. As a result, five alkaloid compounds were identified or tentatively characterized. Among them, the compound 1-deoxynojirimycin (DNJ) was selected as the most typical and active chemical marker and quantified using an improved high performance liquid chromatography (HPLC) normal phase coupled with evaporative light scattering detector (ELSD) method. The developed method was fully validated in terms of linearity, sensitivity, precision and repeatability, as well as recovery, and subsequently applied to evaluate twenty-nine batches of mulberry leaves from different collections. From the analytical data it was discovered that the average content of DNJ is 1.53 mg/g, while the total contents of DNJ in the 29 mulberry leaf sample ranged from 0.20 to 3.88 mg/g, which suggested remarkable differences, although it reached the highest levels in early August. These data may provide an important reference for the quality of mulberry leaves used as herbal medicine for the treatment of diabetes or as a material to obtain the DNJ of α-glucosidase inhibitor or as a functional food. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Comparative Evaluation of Total Antioxidant Capacities of Plant Polyphenols
Molecules 2016, 21(2), 208; doi:10.3390/molecules21020208
Received: 15 January 2016 / Revised: 30 January 2016 / Accepted: 1 February 2016 / Published: 9 February 2016
Cited by 16 | PDF Full-text (1422 KB) | HTML Full-text | XML Full-text
Abstract
Thirty-seven samples of naturally occurring phenolic compounds were evaluated using three common in vitro assays for total antioxidant activity (TAC) testing: the Trolox Equivalent Antioxidant Capacity (TEAC), the Ferric Reducing Antioxidant Potential (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, in addition to
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Thirty-seven samples of naturally occurring phenolic compounds were evaluated using three common in vitro assays for total antioxidant activity (TAC) testing: the Trolox Equivalent Antioxidant Capacity (TEAC), the Ferric Reducing Antioxidant Potential (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, in addition to the Folin-Ciocalteu reagent reactivity (FCR). We found that antioxidant hierarchies depended on the choice of assay and applied ANOVA analyses to explore underlying structure-TAC dependencies. In addition to statistically confirming the empirically established connection between flavonoid ring-B catechol and high TEAC or FRAP, new correlations were also found. In flavonoids, (i) hydroxyl groups on ring-B had a positive effect on all four TAC assays; (ii) the presence of a 3-hydroxyl group on ring-C increased TEAC and FRAP, but had no effect on DPPH or FCR; (iii) Phenolic acids lacking a 3-hydroxyl group had significantly lower FRAP or DPPH than compounds having this structure, while TEAC or FCR were not affected. Results demonstrated that any TAC-based ranking of phenolic rich samples would very much depend on the choice of assay, and argue for use of more than one technique. As an illustration, we compared results of the above four assays using either grapevine leaf extracts or synthetic mixtures of compounds prepared according to major polyphenols identified in the leaves. Full article
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Open AccessArticle Chemical Characterization and Trypanocidal, Leishmanicidal and Cytotoxicity Potential of Lantana camara L. (Verbenaceae) Essential Oil
Molecules 2016, 21(2), 209; doi:10.3390/molecules21020209
Received: 20 December 2015 / Revised: 30 January 2016 / Accepted: 2 February 2016 / Published: 10 February 2016
Cited by 6 | PDF Full-text (214 KB) | HTML Full-text | XML Full-text
Abstract
Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against
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Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against Leishmania braziliensis and Trypanosoma cruzi. The results demonstrated that L. camara essential oil inhibited T. cruzi and L. braziliensis with IC50 of 201.94 μg/mL and 72.31 μg/mL, respectively. L. camara essential oil was found to be toxic to NCTC929 fibroblasts at 500 μg/mL (IC50 = 301.42 μg/mL). The composition of L. camara essential oil analyzed by gas chromatography–mass spectrometry (GC/MS) revealed large amounts of (E)-caryophyllene (23.75%), biciclogermacrene (15.80%), germacrene D (11.73%), terpinolene (6.1%), and sabinene (5.92%), which might be, at least in part, responsible for its activity. Taken together, our results suggest that L. camara essential oil may be an important source of therapeutic agents for the development of alternative drugs against parasitic diseases. Full article
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Open AccessArticle Morphology and N2 Permeance of Sputtered Pd-Ag Ultra-Thin Film Membranes
Molecules 2016, 21(2), 210; doi:10.3390/molecules21020210
Received: 23 December 2015 / Revised: 25 January 2016 / Accepted: 2 February 2016 / Published: 10 February 2016
Cited by 3 | PDF Full-text (2254 KB) | HTML Full-text | XML Full-text
Abstract
The influence of the temperature during the growth of Pd-Ag films by PVD magnetron sputtering onto polished silicon wafers was studied in order to avoid the effect of the support roughness on the layer growth. The surfaces of the Pd-Ag membrane films were
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The influence of the temperature during the growth of Pd-Ag films by PVD magnetron sputtering onto polished silicon wafers was studied in order to avoid the effect of the support roughness on the layer growth. The surfaces of the Pd-Ag membrane films were analyzed by atomic force microscopy (AFM), and the results indicate an increase of the grain size from 120 to 250–270 nm and film surface roughness from 4–5 to 10–12 nm when increasing the temperature from around 360–510 K. After selecting the conditions for obtaining the smallest grain size onto silicon wafer, thin Pd-Ag (0.5–2-µm thick) films were deposited onto different types of porous supports to study the influence of the porous support, layer thickness and target power on the selective layer microstructure and membrane properties. The Pd-Ag layers deposited onto ZrO2 3-nm top layer supports (smallest pore size among all tested) present high N2 permeance in the order of 10−6 mol·m−2·s−1·Pa−1 at room temperature. Full article
(This article belongs to the Special Issue Membrane Catalysis)
Open AccessArticle Inhibition of CYP2B6 by Medicinal Plant Extracts: Implication for Use of Efavirenz and Nevirapine-Based Highly Active Anti-Retroviral Therapy (HAART) in Resource-Limited Settings
Molecules 2016, 21(2), 211; doi:10.3390/molecules21020211
Received: 23 December 2015 / Revised: 25 January 2016 / Accepted: 2 February 2016 / Published: 16 February 2016
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Abstract
Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a
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Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 ± 1.16 µg/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 ± 4.86 µg/mL), Launaea taraxacifolia extract (IC50 = 33.87 ± 1.54 µg/mL), and Boerhavia diffusa extract (IC50 = 34.93 ± 1.06 µg/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 ± 8.71 µg/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts reach the liver, there is a high likelihood of standard doses affecting drug plasma concentrations which could lead to toxicity. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthetic Strategy and Anti-Tumor Activities of Macrocyclic Scaffolds Based on 4-Hydroxyproline
Molecules 2016, 21(2), 212; doi:10.3390/molecules21020212
Received: 10 January 2016 / Revised: 3 February 2016 / Accepted: 4 February 2016 / Published: 15 February 2016
Cited by 1 | PDF Full-text (2036 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells
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A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 µmol/L). Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Constructing a MoS2 QDs/CdS Core/Shell Flowerlike Nanosphere Hierarchical Heterostructure for the Enhanced Stability and Photocatalytic Activity
Molecules 2016, 21(2), 213; doi:10.3390/molecules21020213
Received: 30 November 2015 / Revised: 25 January 2016 / Accepted: 3 February 2016 / Published: 15 February 2016
Cited by 10 | PDF Full-text (2053 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MoS2 quantum dots (QDs)/CdS core/shell nanospheres with a hierarchical heterostructure have been prepared by a simple microwave hydrothermal method. The as-prepared samples are characterized by XRD, TEM, SEM, UV-VIS diffuse reflectance spectra (DRS) and N2-sorption in detail. The photocatalytic activities
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MoS2 quantum dots (QDs)/CdS core/shell nanospheres with a hierarchical heterostructure have been prepared by a simple microwave hydrothermal method. The as-prepared samples are characterized by XRD, TEM, SEM, UV-VIS diffuse reflectance spectra (DRS) and N2-sorption in detail. The photocatalytic activities of the samples are evaluated by water splitting into hydrogen. Results show that the as-prepared MoS2 QDs/CdS core/shell nanospheres with a diameter of about 300 nm are composed of the shell of CdS nanorods and the core of MoS2 QDs. For the photocatalytic reaction, the samples exhibit a high stability of the photocatalytic activity and a much higher hydrogen evolution rate than the pure CdS, the composite prepared by a physical mixture, and the Pt-loaded CdS sample. In addition, the stability of CdS has also been greatly enhanced. The effect of the reaction time on the formations of nanospheres, the photoelectric properties and the photocatalytic activities of the samples has been investigated. Finally, a possible photocatalytic reaction process has also been proposed. Full article
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Open AccessArticle Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene
Molecules 2016, 21(2), 214; doi:10.3390/molecules21020214
Received: 8 January 2016 / Revised: 4 February 2016 / Accepted: 4 February 2016 / Published: 15 February 2016
Cited by 1 | PDF Full-text (1834 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS2 in the presence of K2CO3 under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized
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A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS2 in the presence of K2CO3 under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, 1H-NMR, 13C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1–H1···O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1–H2···O1 and C7–H7A···N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n→π* ICT from LP(1)N5→BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3→ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H···OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle DNA Scaffolded Silver Clusters: A Critical Study
Molecules 2016, 21(2), 216; doi:10.3390/molecules21020216
Received: 28 December 2015 / Revised: 1 February 2016 / Accepted: 2 February 2016 / Published: 17 February 2016
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Abstract
Fluorescent silver nanoclusters (Ag-NCs) are in prominence as novel sensing materials due to their biocompatibility, photostability, and molecule-like optical properties. The present work is carried out on an array (17 sequences) of 16 bases long cytosine rich, single stranded DNA templates 5′-C3
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Fluorescent silver nanoclusters (Ag-NCs) are in prominence as novel sensing materials due to their biocompatibility, photostability, and molecule-like optical properties. The present work is carried out on an array (17 sequences) of 16 bases long cytosine rich, single stranded DNA templates 5′-C3XiC3XiiC3XiiiC3Xiv-3′ where i, ii, iii, iv correspond to T/G/C deoxynucleobases (with default base A). Among all the oligonucleotides, a sequence C3AC3AC3TC3G (3T4G) has been identified, which grows three different near-infrared-emitting NC species with absorption/emission maxima at ~620/700 (species I), 730/800 (species II), and 830 (Species III) nm, respectively. The nature of the spectral profiles, along with relevant parameters namely absorption maximum (\(\lambda_{abs}^{max}\)), emission maximum (\(\lambda_{em}^{max}\)), anisotropy (r), lifetime (\(\tau\)), circular dichroism spectral data are used to understand the microenvironments of the fluorescent NC species I, II, and III. DNA:Ag stiochiometric, pH and solvent dependent studies proved that i-motif scaffolds with different folding topologies are associated with the growth of these three species and a certain concentration of silver and H+ favor the growth of species III. Size exclusion chromatographic measurements provided similar indications that a folded, more compact, classic i-motif template is associated with the formation of the longer NIR (~830 nm) absorbing species. This study provides a more definitive approach to design and obtain a targeted DNA templated Ag-NC with required emission properties for biophysical and cellular applications. Full article
(This article belongs to the Special Issue Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Molecular and Functional Characterization of FLOWERING LOCUS T Homologs in Allium cepa
Molecules 2016, 21(2), 217; doi:10.3390/molecules21020217
Received: 14 December 2015 / Revised: 4 February 2016 / Accepted: 9 February 2016 / Published: 16 February 2016
Cited by 3 | PDF Full-text (2945 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Onion bulbing is an important agricultural trait affecting economic value and is regulated by flowering-related genes. FLOWERING LOCUS T (FT)-like gene function is crucial for the initiation of flowering in various plant species and also in asexual reproduction in tuber plants. By
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Onion bulbing is an important agricultural trait affecting economic value and is regulated by flowering-related genes. FLOWERING LOCUS T (FT)-like gene function is crucial for the initiation of flowering in various plant species and also in asexual reproduction in tuber plants. By employing various computational analysis using RNA-Seq data, we identified eight FT-like genes (AcFT) encoding PEBP (phosphatidylethanolamine-binding protein) domains in Allium cepa. Sequence and phylogenetic analyses of FT-like proteins revealed six proteins that were identical to previously reported AcFT1-6 proteins, as well as one (AcFT7) with a highly conserved region shared with AcFT6 and another (comp106231) with low similarity to MFT protein, but containing a PEBP domain. Homology modelling of AcFT7 proteins showed similar structures and conservation of amino acids crucial for function in AtFT (Arabidopsis) and Hd3a (rice), with variation in the C-terminal region. Further, we analyzed AcFT expression patterns in different transitional stages, as well as under SD (short-day), LD (long-day), and drought treatment in two contrasting genotypic lines EM (early maturation, 36101) and LM (late maturation, 36122). The FT transcript levels were greatly affected by various environmental factors such as photoperiod, temperature and drought. Our results suggest that AcFT7 is a member of the FT-like genes in Allium cepa and may be involved in regulation of onion bulbing, similar to other FT genes. In addition, AcFT4 and AcFT7 could be involved in establishing the difference in timing of bulb maturity between the two contrasting onion lines. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Optimization of Ultrasound-Assisted Extraction of Natural Antioxidants from the Osmanthus fragrans Flower
Molecules 2016, 21(2), 218; doi:10.3390/molecules21020218
Received: 21 December 2015 / Revised: 1 February 2016 / Accepted: 2 February 2016 / Published: 18 February 2016
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Abstract
An ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the Osmanthus fragrans flower. The effect of UAE on antioxidant activity of the extract from the Osmanthus fragrans flower was studied using a Trolox equivalent antioxidant capacity (TEAC) assay. Optimization conditions
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An ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the Osmanthus fragrans flower. The effect of UAE on antioxidant activity of the extract from the Osmanthus fragrans flower was studied using a Trolox equivalent antioxidant capacity (TEAC) assay. Optimization conditions were firstly determined using a single-factor experiment, and response surface methodology was then used to evaluate interaction of several experimental parameters. Analysis of the coefficient of determination showed that second-order polynomial models produced a highly satisfactory fitting of the experimental data with regard to TEAC values (R2 = 0.9829, p < 0.0001). The optimal conditions were 39.1% ethanol, and extraction for 35.2 min at 59.4 °C. Under these conditions, the maximum TEAC value was 584.9 ± 6.0 μmol Trolox/g DW, which was higher than those obtained by the conventional extracting method (486.4 ± 12.6 μmol Trolox/g DW) and the Soxhlet extraction method (339.1 ± 16.2 μmol Trolox/g DW). The crude extract obtained could be used either as a food additive or in pharmaceuticals for the prevention and treatment of diseases caused by oxidative stress. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Comparison of Properties among Dendritic and Hyperbranched Poly(ether ether ketone)s and Linear Poly(ether ketone)s
Molecules 2016, 21(2), 219; doi:10.3390/molecules21020219
Received: 18 December 2015 / Revised: 28 January 2016 / Accepted: 5 February 2016 / Published: 16 February 2016
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Abstract
Poly(ether ether ketone) dendrimers and hyperbranched polymers were prepared from 3,5-dimethoxy-4′-(4-fluorobenzoyl)diphenyl ether and 3,5-dihydroxy-4′-(4-fluorobenzoyl)diphenyl ether through aromatic nucleophilic substitution reactions. 1-(tert-Butyldimethylsiloxy)-3,5-bis(4-fluorobenzoyl)benzene was polycondensed with bisphenols, followed by cleavage of the protective group to form linear poly(ether ketone)s having the same hydroxyl
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Poly(ether ether ketone) dendrimers and hyperbranched polymers were prepared from 3,5-dimethoxy-4′-(4-fluorobenzoyl)diphenyl ether and 3,5-dihydroxy-4′-(4-fluorobenzoyl)diphenyl ether through aromatic nucleophilic substitution reactions. 1-(tert-Butyldimethylsiloxy)-3,5-bis(4-fluorobenzoyl)benzene was polycondensed with bisphenols, followed by cleavage of the protective group to form linear poly(ether ketone)s having the same hydroxyl groups in the side chains as the chain ends of the dendrimer and hyperbranched polymers. Their properties, such as solubilities, reduced viscosities, and thermal properties, were compared with one another. Similar comparisons were also carried out among the corresponding methoxy group polymers, and the size of the molecules was shown to affect the properties. Full article
(This article belongs to the Special Issue Functional Dendrimers)
Open AccessArticle Bioactive ZnO Coatings Deposited by MAPLE—An Appropriate Strategy to Produce Efficient Anti-Biofilm Surfaces
Molecules 2016, 21(2), 220; doi:10.3390/molecules21020220
Received: 12 January 2016 / Revised: 3 February 2016 / Accepted: 5 February 2016 / Published: 16 February 2016
Cited by 5 | PDF Full-text (1958 KB) | HTML Full-text | XML Full-text
Abstract
Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was
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Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was correlated with an increased anti-biofilm activity of ZnO/CD/Cfp composites. In vitro and in vivo tests have revealed a good biocompatibility of ZnO/CD/Cfp coatings, which recommend them as competitive candidates for the development of antimicrobial surfaces with biomedical applications. The release of the fourth generation cephalosporin Cfp in a biologically active form from the ZnO matrix could help preventing the bacterial adhesion and the subsequent colonization and biofilm development on various surfaces, and thus decreasing the risk of biofilm-related infections. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM) Analyses
Molecules 2016, 21(2), 222; doi:10.3390/molecules21020222
Received: 5 January 2016 / Revised: 28 January 2016 / Accepted: 1 February 2016 / Published: 17 February 2016
Cited by 8 | PDF Full-text (6830 KB) | HTML Full-text | XML Full-text
Abstract
Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6–8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic
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Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6–8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, 1H-13C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn’t guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics. Full article
(This article belongs to the Section Bioorganic Chemistry)
Open AccessArticle Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum
Molecules 2016, 21(2), 223; doi:10.3390/molecules21020223
Received: 18 December 2015 / Revised: 29 January 2016 / Accepted: 2 February 2016 / Published: 17 February 2016
PDF Full-text (1813 KB) | HTML Full-text | XML Full-text
Abstract
The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation
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The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation of new antiplasmodial drug leads. One of the promising compounds is TCMDC-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical properties. Several new analogues based on a 2-phenoxyanilide scaffold were synthesized by standard amide coupling reactions and were fully characterized regarding their identity and purity by spectroscopic and chromatographic methods. Furthermore, the results of the biological evaluation of all congeners against Plasmodium falciparum NF54 strains are presented. The findings of our in vitro screening could not confirm the presumed nanomolar antiplasmodial activity of TCMDC-137332 and its derivatives. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Conjugated Oligo-Aromatic Compounds Bearing a 3,4,5-Trimethoxy Moiety: Investigation of Their Antioxidant Activity Correlated with a DFT Study
Molecules 2016, 21(2), 224; doi:10.3390/molecules21020224
Received: 8 January 2016 / Revised: 4 February 2016 / Accepted: 5 February 2016 / Published: 17 February 2016
Cited by 4 | PDF Full-text (2349 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of heterocyclic compounds bearing the well-known free radical scavenging 3,4,5-trimethoxybenzyloxy group, was synthesized. The key compound 4-(3,4,5-trimethoxybenzyl-oxy)benzohydrazide was converted into thiosemicarbazide derivatives, which were subsequently cyclized with NaOH to provide 1,2,4-triazole derivatives. Alternative treatment of the acid hydrazide with carbon disulfide
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A series of heterocyclic compounds bearing the well-known free radical scavenging 3,4,5-trimethoxybenzyloxy group, was synthesized. The key compound 4-(3,4,5-trimethoxybenzyl-oxy)benzohydrazide was converted into thiosemicarbazide derivatives, which were subsequently cyclized with NaOH to provide 1,2,4-triazole derivatives. Alternative treatment of the acid hydrazide with carbon disulfide in the presence of KOH led to the corresponding 1,3,4-oxadiazole and various alkylated derivatives. The newly synthesized compounds were purified and the structures of the products were elucidated and confirmed on the basis of their analytical and spectral data. Their antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assays. The thiosemicarbazide derivatives were highly active in both antioxidant assays with the lowest IC50 value for DPPH radical scavenging. Theoretical calculations based on density functional theory (DFT) were performed to understand the relative importance of NH, SH and CH hydrogens on the radical scavenging activities of these compounds. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Antimicrobial Activity and Stability of Short and Long Based Arachnid Synthetic Peptides in the Presence of Commercial Antibiotics
Molecules 2016, 21(2), 225; doi:10.3390/molecules21020225
Received: 20 November 2015 / Revised: 28 January 2016 / Accepted: 3 February 2016 / Published: 17 February 2016
Cited by 2 | PDF Full-text (7964 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Four antimicrobial peptides (AMPs) named Pin2[G], Pin2[14], P18K and FA1 were chemically synthesized and purified. The four peptides were evaluated in the presence of eight commercial antibiotics against four microorganisms of medical importance: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and
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Four antimicrobial peptides (AMPs) named Pin2[G], Pin2[14], P18K and FA1 were chemically synthesized and purified. The four peptides were evaluated in the presence of eight commercial antibiotics against four microorganisms of medical importance: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The commercial antibiotics used were amoxicillin, azithromycin, ceftriaxone, gentamicin, levofloxacin, sulfamethoxazole, trimethoprim and vancomycin. The best AMP against P. aeruginosa was the peptide FA1, and the best AMP against S. aureus was Pin2[G]. Both FA1 and Pin2[G] were efficient against E. coli, but they were not effective against K. pneumoniae. As K. pneumoniae was resistant to most of the commercial antibiotics, combinations of the AMPs FA1 and Pin2[G] were prepared with these antibiotics. According to the fractional inhibitory concentration (FIC) index, the best antimicrobial combinations were obtained with concomitant applications of mixtures of FA1 with levofloxacin and sulfamethoxazole. However, combinations of FA1 or Pin2[G] with other antibiotics showed that total inhibitory effect of the combinations were greater than the sum of the individual effects of either the antimicrobial peptide or the antibiotic. We also evaluated the stability of the AMPs. The AMP Pin2[G] manifested the best performance in saline buffer, in supernatants of bacterial growth and in human blood plasma. Nevertheless, all AMPs were cleaved using endoproteolytic enzymes. These data show advantages and disadvantages of AMPs for potential clinical treatments of bacterial infections, using them in conjunction with commercial antibiotics. Full article
Open AccessArticle Screening of Korean Natural Products for Anti-Adipogenesis Properties and Isolation of Kaempferol-3-O-rutinoside as a Potent Anti-Adipogenetic Compound from Solidago virgaurea
Molecules 2016, 21(2), 226; doi:10.3390/molecules21020226
Received: 14 December 2015 / Revised: 6 February 2016 / Accepted: 9 February 2016 / Published: 17 February 2016
Cited by 8 | PDF Full-text (5215 KB) | HTML Full-text | XML Full-text
Abstract
In this study, the anti-adipogenetic activity of 300 plant extracts was investigated using an Oil Red O staining assay in a 3T3-L1 cell line. Our results indicate that three plants, including the stem and leaf of Physalis angulata, the whole grass of
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In this study, the anti-adipogenetic activity of 300 plant extracts was investigated using an Oil Red O staining assay in a 3T3-L1 cell line. Our results indicate that three plants, including the stem and leaf of Physalis angulata, the whole grass of Solidago virgaurea, and the root of Dioscorea nipponica, produced over 90% inhibition of adipogenesis. Kaempferol-3-O-rutinoside, which demonstrated a 48.2% inhibitory effect on adipogenesis without cytotoxicity, was isolated from the butanol layer of a water extract of S. virgaurea guided by the anti-adipogenesis assay in 3T3-L1. PPAR-γ and C/EBPα expression levels were determined using western blot, and our results indicate that kaempferol-3-O-rutinoside has a strong anti-adipogenic effect in 3T3-L1 cells through the suppression of increases in PPAR-γ and C/EBPα expression. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Screening and Analysis of the Potential Bioactive Components of Poria cocos (Schw.) Wolf by HPLC and HPLC-MSn with the Aid of Chemometrics
Molecules 2016, 21(2), 227; doi:10.3390/molecules21020227
Received: 21 December 2015 / Revised: 3 February 2016 / Accepted: 3 February 2016 / Published: 18 February 2016
Cited by 5 | PDF Full-text (1377 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the present study was to establish a new method based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) to determine the quality of different samples of Poria cocos (Schw.) Wolf obtained from Yunnan, Hubei, Guizhou, Fujian,
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The aim of the present study was to establish a new method based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) to determine the quality of different samples of Poria cocos (Schw.) Wolf obtained from Yunnan, Hubei, Guizhou, Fujian, Henan, Guangxi, Anhui and Sichuan in China. For this purpose 15 samples from the different habitats were analyzed by HPLC-PAD and HPLC-MSn. Twenty-three compounds were detected by HPLC-MSn, of which twenty compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. The characteristic fragmentations were summarized. 3-epi-Dehydrotumulosic acid (F13), 3-oxo-16α,25-dihydroxylanosta-7,9(11),24(31)-trien-21-oic acid (F4), 3-oxo-6,16α-dihydroxylanosta-7,9(11),24(31)-trien-21-oic acid (F7) and dehydropachymic acid (F15) were deemed to be suitable marker compounds to distinguish between samples of different quality according to CA and PCA. This study provides helpful chemical information for further anti-tumor activity and active mechanism research on P. cocos. The results proved that fingerprint combined with a chemometric approach is a simple, rapid and effective method for the quality discrimination of P. cocos. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus
Molecules 2016, 21(2), 228; doi:10.3390/molecules21020228
Received: 21 January 2016 / Revised: 4 February 2016 / Accepted: 4 February 2016 / Published: 18 February 2016
Cited by 2 | PDF Full-text (880 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new conjugated compounds with a –SCH2– linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole–coumarin conjugates, three of them exhibited appealing EC50 values (5.1–8.4
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A series of new conjugated compounds with a –SCH2– linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole–coumarin conjugates, three of them exhibited appealing EC50 values (5.1–8.4 μM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase
Molecules 2016, 21(2), 229; doi:10.3390/molecules21020229
Received: 22 December 2015 / Revised: 12 February 2016 / Accepted: 14 February 2016 / Published: 18 February 2016
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Abstract
Fatty Acid Amide Hydrolase (FAAH) is an intracellular serine enzyme involved in the biological degradation of the fatty acid ethanolamide family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-carboxamide scaffold was confirmed as a
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Fatty Acid Amide Hydrolase (FAAH) is an intracellular serine enzyme involved in the biological degradation of the fatty acid ethanolamide family of signaling lipids, which exerts neuroprotective, anti-inflammatory, and analgesic properties. In the present study, a conjugated 2,4-dioxo-pyrimidine-1-carboxamide scaffold was confirmed as a novel template for FAAH inhibitors, based on which, a series of analogues had been prepared for an initial structure-activity relationship (SAR) study. Most of the synthesized compounds displayed moderate to significant FAAH inhibitory potency. Among them, compounds 11 and 14 showed better activity than others, with IC50 values of 21 and 53 nM. SAR analysis indicated that 2,4-dioxopyrimidine-1-carboxamides represented a novel class of potent inhibitors of FAAH, and substitution at the uracil ring or replacement of the N-terminal group might favor the inhibitory potency. Selected compounds of this class may be used as useful parent molecules for further investigation. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle New 3-Cyano-2-Substituted Pyridines Induce Apoptosis in MCF 7 Breast Cancer Cells
Molecules 2016, 21(2), 230; doi:10.3390/molecules21020230
Received: 3 January 2016 / Revised: 1 February 2016 / Accepted: 1 February 2016 / Published: 18 February 2016
Cited by 4 | PDF Full-text (2422 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of new 3-cyano-2-substituted pyridines bearing various pharmacophores and functionalities at position 2 is described. The synthesized compounds were evaluated for their in vitro anti-cancer activities on five cancer cell lines using 5-FU as reference compound. The results revealed that the benzohydrazide
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The synthesis of new 3-cyano-2-substituted pyridines bearing various pharmacophores and functionalities at position 2 is described. The synthesized compounds were evaluated for their in vitro anti-cancer activities on five cancer cell lines using 5-FU as reference compound. The results revealed that the benzohydrazide derivative 9a induced growth inhibition in human breast cancer cell line MCF-7 with an IC50 value of 2 μM and it showed lower cytotoxicity on MCF-12a normal breast epithelial cells. Additionally, 9a induced apoptotic morphological changes and induced apoptosis in MCF-7 in a dose and time-dependent manner according to an enzyme linked immunosorbent apoptosis assay which is further confirmed by a TUNEL assay. Flow cytometric analysis indicated that 9a arrested MCF-7 cells in the G1 phase, which was further confirmed by increased expression of p21 and p27 and reduced expression of CDK2 and CDK4. Western blot data revealed significant upregulation of the expression of p53, Bax, caspase-3 and down-regulation of Bcl-2, Mdm-2 and Akt. Additionally, 9a increased the release of cytochrome c from mitochondria to cytoplasm which provokes the mitochondrial apoptotic pathway while it showed no significant change on the expression of the death receptor proteins procaspase-8, caspase-8 and FAS. Furthermore, 9a reduced the expression of phospho AKT and β-catenin in dose dependent manner while inhibiting the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). Our findings suggest that compound 9a could be considered as a lead structure for further development of more potent apoptosis inducing agents with anti-metastatic activities. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Bioadhesive Surfactant Systems for Methotrexate Skin Delivery
Molecules 2016, 21(2), 231; doi:10.3390/molecules21020231
Received: 23 December 2015 / Revised: 2 February 2016 / Accepted: 5 February 2016 / Published: 18 February 2016
Cited by 7 | PDF Full-text (1557 KB) | HTML Full-text | XML Full-text
Abstract
Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME)
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Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME) and a liquid crystalline system (LCS), consisting of a glycol copolymer-based silicone fluid (SFGC) as oil phase, polyether functional siloxane (PFS) as surfactant, and carbomer homopolymer type A (C971) dispersion at 0.5% (wt/wt) as aqueous phase. Polarized light microscopy and small-angle X-ray scattering evidenced the presence of hexagonal and lamellar LCSs, and also a ME. Texture profile and in vitro bioadhesion assays showed that these formulations are suitable for topical application, showing interesting hardness, adhesiveness and compressibility values. Rheology analysis confirmed the Newtonian behaviour of the ME, whereas lamellar and hexagonal LCSs behave as pseudoplastic and dilatant non-Newtonian fluids, respectively. In vitro release profiles indicated that MTX could be released in a controlled manner from all the systems, and the Weibull model showed the highest adjusted coefficient of determination. Finally, the formulations were not cytotoxic to the immortalized human keratinocyte line HaCaT. Therefore, these bioadhesive surfactant systems established with PFS and C971 have great potential as skin delivery systems. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Influence of Thermal Treatment Conditions on the Properties of Dental Silicate Cements
Molecules 2016, 21(2), 233; doi:10.3390/molecules21020233
Received: 25 January 2016 / Revised: 9 February 2016 / Accepted: 13 February 2016 / Published: 18 February 2016
Cited by 1 | PDF Full-text (7542 KB) | HTML Full-text | XML Full-text
Abstract
In this study the sol-gel process was used to synthesize a precursor mixture for the preparation of silicate cement, also called mineral trioxide aggregate (MTA) cement. This mixture was thermally treated under two different conditions (1400 °C/2 h and 1450 °C/3 h) followed
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In this study the sol-gel process was used to synthesize a precursor mixture for the preparation of silicate cement, also called mineral trioxide aggregate (MTA) cement. This mixture was thermally treated under two different conditions (1400 °C/2 h and 1450 °C/3 h) followed by rapid cooling in air. The resulted material (clinker) was ground for one hour in a laboratory planetary mill (v = 150 rot/min), in order to obtain the MTA cements. The setting time and mechanical properties, in vitro induction of apatite formation by soaking in simulated body fluid (SBF) and cytocompatibility of the MTA cements were assessed in this study. The hardening processes, nature of the reaction products and the microstructural characteristics were also investigated. The anhydrous and hydrated cements were characterized by different techniques e.g., X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared spectroscopy (FT-IR) and thermal analysis (DTA-DTG-TG). The setting time of the MTA cement obtained by thermal treatment at 1400 °C/2 h (MTA1) was 55 min and 15 min for the MTA cement obtained at 1450 °C/3 h (MTA2). The compressive strength values were 18.5 MPa (MTA1) and 22.9 MPa (MTA2). Both MTA cements showed good bioactivity (assessed by an in vitro test), good cytocompatibility and stimulatory effect on the proliferation of cells. Full article
(This article belongs to the Special Issue Pharmaceutical Nanotechnology: Novel Approaches)
Open AccessArticle Multicomponent Analysis of the Differential Induction of Secondary Metabolite Profiles in Fungal Endophytes
Molecules 2016, 21(2), 234; doi:10.3390/molecules21020234
Received: 10 November 2015 / Revised: 10 February 2016 / Accepted: 13 February 2016 / Published: 18 February 2016
Cited by 7 | PDF Full-text (3847 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles
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Small molecule histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors are commonly used to perturb the production of fungal metabolites leading to the induction of the expression of silent biosynthetic pathways. Several reports have described the variable effects observed in natural product profiles in fungi treated with HDAC and DNMT inhibitors, such as enhanced chemical diversity and/or the induction of new molecules previously unknown to be produced by the strain. Fungal endophytes are known to produce a wide variety of secondary metabolites (SMs) involved in their adaptation and survival within higher plants. The plant-microbe interaction may influence the expression of some biosynthetic pathways, otherwise cryptic in these fungi when grown in vitro. The aim of this study was to setup a systematic approach to evaluate and identify the possible effects of HDAC and DNMT inhibitors on the metabolic profiles of wild type fungal endophytes, including the chemical identification and characterization of the most significant SMs induced by these epigenetic modifiers. Full article
(This article belongs to the Special Issue Applications of Metabolomics within Natural Products Chemistry)
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Open AccessArticle Characterizing the Solvated Structure of Photoexcited [Os(terpy)2]2+ with X-ray Transient Absorption Spectroscopy and DFT Calculations
Molecules 2016, 21(2), 235; doi:10.3390/molecules21020235
Received: 17 January 2016 / Revised: 12 February 2016 / Accepted: 15 February 2016 / Published: 19 February 2016
Cited by 5 | PDF Full-text (2173 KB) | HTML Full-text | XML Full-text
Abstract
Characterizing the geometric and electronic structures of individual photoexcited dye molecules in solution is an important step towards understanding the interfacial properties of photo-active electrodes. The broad family of “red sensitizers” based on osmium(II) polypyridyl compounds often undergoes small photo-induced structural changes which
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Characterizing the geometric and electronic structures of individual photoexcited dye molecules in solution is an important step towards understanding the interfacial properties of photo-active electrodes. The broad family of “red sensitizers” based on osmium(II) polypyridyl compounds often undergoes small photo-induced structural changes which are challenging to characterize. In this work, X-ray transient absorption spectroscopy with picosecond temporal resolution is employed to determine the geometric and electronic structures of the photoexcited triplet state of [Os(terpy)2]2+ (terpy: 2,2′:6′,2″-terpyridine) solvated in methanol. From the EXAFS analysis, the structural changes can be characterized by a slight overall expansion of the first coordination shell [OsN6]. DFT calculations supports the XTA results. They also provide additional information about the nature of the molecular orbitals that contribute to the optical spectrum (with TD-DFT) and the near-edge region of the X-ray spectra. Full article
(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)
Open AccessArticle Antifungal Activity of Isoliquiritin and Its Inhibitory Effect against Peronophythora litchi Chen through a Membrane Damage Mechanism
Molecules 2016, 21(2), 237; doi:10.3390/molecules21020237
Received: 17 January 2016 / Revised: 13 February 2016 / Accepted: 14 February 2016 / Published: 19 February 2016
Cited by 4 | PDF Full-text (1634 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the antifungal activity and potential antifungal mechanism(s) of isoliquiritin against P. litchi Chen, one of the main litchi pathogens. The antifungal activity of isoliquiritin against P. litchi Chen had been proven in a dose-dependent manner through in vitro (mycelial growth
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This study investigated the antifungal activity and potential antifungal mechanism(s) of isoliquiritin against P. litchi Chen, one of the main litchi pathogens. The antifungal activity of isoliquiritin against P. litchi Chen had been proven in a dose-dependent manner through in vitro (mycelial growth and sporangia germination) and in vivo (detached leaf) tests. Results revealed that isoliquiritin exhibited significant antifungal activity against the tested pathogens, especially, P. litchi Chen, with a minimum inhibitory concentration of 27.33 mg/L. The morphology of P. litchi Chen was apparently changed by isoliquiritin through cytoplasm leakage and distortion of mycelia. The cell membrane permeability of the P. litchi Chen increased with the increasing concentration of isoliquiritin, as evidenced by a rise in relative electric conductivity and a decrease in reducing sugar contents. These results indicated that the antifungal effects of isoliquiritin could be explained by a membrane lesion mechanism causing damage to the cell membrane integrity leading to the death of mycelial cells. Taken together, isoliquiritin may be used as a natural alternative to commercial fungicides or a lead compound to develop new fungicides for the control of litchi downy blight. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of 2-Alkenyl-2H-indazoles from 2-(2-Carbonylmethyl)-2H-indazoles
Molecules 2016, 21(2), 238; doi:10.3390/molecules21020238
Received: 27 January 2016 / Revised: 13 February 2016 / Accepted: 15 February 2016 / Published: 19 February 2016
PDF Full-text (3645 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A procedure has been developed for synthesis of 2-alkenyl-2H-indazoles starting from 2-(2-carbonylmethyl)-2H-indazoles, which are prepared by gallium/aluminium- and aluminium-mediated, direct, regioselective alkylation of indazoles with α-bromocarbonyl compounds. The structure of 3-(2H-indazol-2-yl)-2H-chromen-2-one was proven by X-ray
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A procedure has been developed for synthesis of 2-alkenyl-2H-indazoles starting from 2-(2-carbonylmethyl)-2H-indazoles, which are prepared by gallium/aluminium- and aluminium-mediated, direct, regioselective alkylation of indazoles with α-bromocarbonyl compounds. The structure of 3-(2H-indazol-2-yl)-2H-chromen-2-one was proven by X-ray crystallography. The styrene- and coumarin-2H-indazoles produced by using the new method were found to have interesting fluorescence properties. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram-Positive Pathogens: 2-(2-Phenylhydrazinylidene)alkanoic Acids and Related Derivatives
Molecules 2016, 21(2), 241; doi:10.3390/molecules21020241
Received: 26 December 2015 / Revised: 5 February 2016 / Accepted: 12 February 2016 / Published: 19 February 2016
Cited by 6 | PDF Full-text (923 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for
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A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 µM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compound resulted 2a, which showed inhibition of about 60% against S. aureus ATCC 29213, S. aureus ATCC 25923, S. aureus ATCC 6538 and S. epidermidis RP62A at a screening concentration of 100 µM. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessFeature PaperArticle Porphyrin Cobalt(III) “Nitrene Radical” Reactivity; Hydrogen Atom Transfer from Ortho-YH Substituents to the Nitrene Moiety of Cobalt-Bound Aryl Nitrene Intermediates (Y = O, NH)
Molecules 2016, 21(2), 242; doi:10.3390/molecules21020242
Received: 16 January 2016 / Revised: 5 February 2016 / Accepted: 16 February 2016 / Published: 20 February 2016
Cited by 3 | PDF Full-text (5674 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the field of cobalt(II) porphyrin-catalyzed metallo-radical reactions, organic azides have emerged as successful nitrene transfer reagents. In the pursuit of employing ortho-YH substituted (Y = O, NH) aryl azides in Co(II) porphyrin-catalyzed nitrene transfer reactions, unexpected hydrogen atom transfer (HAT) from
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In the field of cobalt(II) porphyrin-catalyzed metallo-radical reactions, organic azides have emerged as successful nitrene transfer reagents. In the pursuit of employing ortho-YH substituted (Y = O, NH) aryl azides in Co(II) porphyrin-catalyzed nitrene transfer reactions, unexpected hydrogen atom transfer (HAT) from the OH or NH2 group in the ortho-position to the nitrene moiety of the key radical-intermediate was observed. This leads to formation of reactive ortho-iminoquinonoid (Y = O) and phenylene diimine (Y = NH) species. These intermediates convert to subsequent products in non-catalyzed reactions, as is typical for these free organic compounds. As such, the observed reactions prevent the anticipated cobalt-mediated catalytic radical-type coupling of the nitrene radical intermediates to alkynes or alkenes. Nonetheless, the observed reactions provide valuable insights into the reactivity of transition metal nitrene-radical intermediates, and give access to ortho-iminoquinonoid and phenylene diimine intermediates from ortho-YH substituted aryl azides in a catalytic manner. The latter can be employed as intermediates in one-pot catalytic transformations. From the ortho-hydroxy aryl azide substrates both phenoxizinones and benzoxazines could be synthesized in high yields. From the ortho-amino aryl azide substrates azabenzene compounds were obtained as the main products. Computational studies support these observations, and reveal that HAT from the neighboring OH and NH2 moiety to the nitrene radical moiety has a low energy barrier. Full article
(This article belongs to the Special Issue Organic Azides)
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Open AccessArticle Catechin Hydrate Augments the Antibacterial Action of Selected Antibiotics against Staphylococcus aureus Clinical Strains
Molecules 2016, 21(2), 244; doi:10.3390/molecules21020244
Received: 17 December 2015 / Revised: 9 February 2016 / Accepted: 18 February 2016 / Published: 20 February 2016
Cited by 2 | PDF Full-text (224 KB) | HTML Full-text | XML Full-text
Abstract
Synergistic effects between commonly used antibiotics and natural substances may be an alternative to conventional antibacterial therapies. The objective of the presented study was to assess the in vitro antibacterial activity of catechin hydrate (CH) and evaluate the interactions of CH with selected
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Synergistic effects between commonly used antibiotics and natural substances may be an alternative to conventional antibacterial therapies. The objective of the presented study was to assess the in vitro antibacterial activity of catechin hydrate (CH) and evaluate the interactions of CH with selected antibiotics using Staphylococcus aureus clinical and reference strains. CH displayed diverse activity towards examined S. aureus strains, with minimal inhibitory concentrations (MICs) ranging from 256 to 2048 µg/mL. The interaction between CH and antibiotics was assessed by an E-test. The most significant synergistic effects were noticed for CH in combination with clindamycin and erythromycin. For cefoxitin and vancomycin a decrease of MIC values in the presence of CH was also observed, but it did not reach statistical significance. The obtained results demonstrate that CH shows antimicrobial activity against Staphylococcus aureus clinical strains. What is more, we proved a synergistic effect of CH with erythromycin and clindamycin. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Leccinum molle (Bon) Bon and Leccinum vulpinum Watling: The First Study of Their Nutritional and Antioxidant Potential
Molecules 2016, 21(2), 246; doi:10.3390/molecules21020246
Received: 21 December 2015 / Revised: 7 February 2016 / Accepted: 18 February 2016 / Published: 20 February 2016
PDF Full-text (627 KB) | HTML Full-text | XML Full-text
Abstract
This work presents the chemical profile of two edible species of mushrooms from the genus Leccinum: Leccinum molle (Bon) Bon and Leccinum vulpinum Watling, both harvested on the outskirts of Bragança (Northeastern Portugal). Both species were prepared and characterized regarding their content in
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This work presents the chemical profile of two edible species of mushrooms from the genus Leccinum: Leccinum molle (Bon) Bon and Leccinum vulpinum Watling, both harvested on the outskirts of Bragança (Northeastern Portugal). Both species were prepared and characterized regarding their content in nutrients (i.e., free sugars, fatty acids and vitamins), non-nutrients (i.e., phenolic and other organic acids) and antioxidant activity. To the best of our knowledge, no previous studies on the chemical characterization and bioactivity of these species have been undertaken. Accordingly, this study intends to increase the available information concerning edible mushroom species, as well as to highlight another important factor regarding the conservation of the mycological resources—their potential as sources of nutraceutical/pharmaceutical compounds. Overall, both species revealed similar nutrient profiles, with low fat levels, fructose, mannitol and trehalose as the foremost free sugars, and high percentages of mono- and polyunsaturated fatty acids. They also revealed the presence of bioactive compounds, namely phenolic (e.g., gallic acid, protocatechuic acid and p-hydroxybenzoic acid) and organic acids (e.g., citric and fumaric acids) and presented antioxidant properties. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis and Characterization of Some New Coumarins with in Vitro Antitumor and Antioxidant Activity and High Protective Effects against DNA Damage
Molecules 2016, 21(2), 249; doi:10.3390/molecules21020249
Received: 23 December 2015 / Revised: 2 February 2016 / Accepted: 17 February 2016 / Published: 22 February 2016
Cited by 6 | PDF Full-text (1542 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Coumarins are naturally occurring oxygen heterocyclic compounds having multifarious medicinal properties, hence used as lead compounds for designing new potent analogs. The chromene butenoic acid 3 and the benzochromene butenoic acid 4 which are derived from the reaction of glyoxalic acid with 3-acetylcoumarin
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Coumarins are naturally occurring oxygen heterocyclic compounds having multifarious medicinal properties, hence used as lead compounds for designing new potent analogs. The chromene butenoic acid 3 and the benzochromene butenoic acid 4 which are derived from the reaction of glyoxalic acid with 3-acetylcoumarin and 3-acetylbenzocoumarin, respectively, were reacted with different nitrogen and carbon nucleophiles to give new heterocyclic compounds. The structures of the prepared compounds were elucidated by IR, 1H-NMR, and mass spectroscopy. Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines namely; hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity. Full article
(This article belongs to the Special Issue Coumarins, Xanthones and Related Compounds)
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Open AccessArticle Multicomponent Synthesis and Evaluation of New 1,2,3-Triazole Derivatives of Dihydropyrimidinones as Acidic Corrosion Inhibitors for Steel
Molecules 2016, 21(2), 250; doi:10.3390/molecules21020250
Received: 23 December 2015 / Revised: 7 February 2016 / Accepted: 17 February 2016 / Published: 22 February 2016
Cited by 5 | PDF Full-text (1591 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which
[...] Read more.
An efficient one-pot synthesis of 1,2,3-triazole derivatives of dihydropyrimidinones has been developed using two multicomponent reactions. The aldehyde-1,2,3-triazoles were obtained in good yields from in situ-generated organic azides and O-propargylbenzaldehyde. The target heterocycles were synthesized through the Biginelli reaction in which the aldehyde-1,2,3-triazoles reacted with ethyl acetoacetate and urea in the presence of Ce(OTf)3 as the catalyst. The corrosion inhibition of steel grade API 5 L X52 in 1 M HCl by the synthesized compounds was investigated using the electrochemical impedance spectroscopy technique. The measurements revealed that these heterocycles are promising candidates to inhibit acidic corrosion of steel. Full article
(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)
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Open AccessArticle Phenolics from Garcinia mangostana Inhibit Advanced Glycation Endproducts Formation: Effect on Amadori Products, Cross-Linked Structures and Protein Thiols
Molecules 2016, 21(2), 251; doi:10.3390/molecules21020251
Received: 23 January 2016 / Revised: 17 February 2016 / Accepted: 18 February 2016 / Published: 22 February 2016
Cited by 6 | PDF Full-text (3574 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine
[...] Read more.
Accumulation of Advanced Glycation Endproducts (AGEs) in body tissues plays a major role in the development of diabetic complications. Here, the inhibitory effect of bioactive metabolites isolated from fruit hulls of Garcinia mangostana on AGE formation was investigated through bio-guided approach using aminoguanidine (AG) as a positive control. Including G. mangostana total methanol extract (GMT) in the reaction mixture of bovine serum albumin (BSA) and glucose or ribose inhibited the fluorescent and non-fluorescent AGEs formation in a dose dependent manner. The bioassay guided fractionation of GMT revealed isolation of four bioactive constituents from the bioactive fraction; which were identified as: garcimangosone D (1), aromadendrin-8-C-glucopyranoside (2), epicatechin (3), and 2,3′,4,5′,6-pentahydroxybenzophenone (4). All the tested compounds significantly inhibited fluorescent and non-fluorescent AGEs formation in a dose dependent manner whereas compound 3 (epicatechin) was found to be the most potent. In search for the level of action, addition of GMT, and compounds 2–4 inhibited fructosamine (Amadori product) and protein aggregation formation in both glucose and ribose. To explore the mechanism of action, it was found that addition of GMT and only compound (3) to reaction mixture increased protein thiol in both glucose and ribose while compounds 1, 2 and 4 only increased thiol in case of ribose. In conclusion, phenolic compounds 1–4 inhibited AGEs formation at the levels of Amadori product and protein aggregation formation through saving protein thiol. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis of Oxylipin Mimics and Their Antifungal Activity against the Citrus Postharvest Pathogens
Molecules 2016, 21(2), 254; doi:10.3390/molecules21020254
Received: 29 September 2015 / Revised: 7 January 2016 / Accepted: 13 January 2016 / Published: 22 February 2016
Cited by 1 | PDF Full-text (628 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nine oxylipin mimics were designed and synthesized starting from d-mannose. Their antifungal activity against three citrus postharvest pathogens was evaluated by spore germination assay. The results indicated that all the compounds significantly inhibited the growth of Penicillium digitatum, Penicillium italicum and
[...] Read more.
Nine oxylipin mimics were designed and synthesized starting from d-mannose. Their antifungal activity against three citrus postharvest pathogens was evaluated by spore germination assay. The results indicated that all the compounds significantly inhibited the growth of Penicillium digitatum, Penicillium italicum and Aspergillus niger. The compound (3Z,6Z,8S,9R,10R)-octadeca-3,6-diene-8,9,10-triol (3) exhibited excellent inhibitory effect on both Penicillium digitatum (IC50 = 34 ppm) and Penicillium italicum (IC50 = 94 ppm). Their in vivo antifungal activities against citrus postharvest blue mold were tested with fruit inoculated with the pathogen Penicillium italicum. The compound (3R,4S)-methyl 3,4-dihydroxy-5-octyltetrahydrofuran-2-carboxylate (9) demonstrated significant efficacy by reducing the disease severity to 60%. The antifungal mechanism of these oxylipin mimics was postulated in which both inhibition of pathogenic mycelium and stimuli of the host oxylipin-mediated defense response played important roles. Full article
(This article belongs to the Section Bioorganic Chemistry)
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Open AccessReview Recent Advances in the Emission and Functions of Plant Vegetative Volatiles
Molecules 2016, 21(2), 124; doi:10.3390/molecules21020124
Received: 25 December 2015 / Revised: 11 January 2016 / Accepted: 13 January 2016 / Published: 22 January 2016
Cited by 16 | PDF Full-text (1831 KB) | HTML Full-text | XML Full-text
Abstract
Plants synthesize and emit a large variety of volatile organic compounds, which possess extremely important ecological functions. In most case, most plant volatiles are liquids, rather than gases, at room temperature. Some volatiles are emitted “on demand” when plants, especially vegetative parts, are
[...] Read more.
Plants synthesize and emit a large variety of volatile organic compounds, which possess extremely important ecological functions. In most case, most plant volatiles are liquids, rather than gases, at room temperature. Some volatiles are emitted “on demand” when plants, especially vegetative parts, are exposed to abiotic or biotic stress. In this review, we summarize some of the highlights of plant vegetative volatile emission and functions research published during the past few years. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
Open AccessReview Preventive and Therapeutic Effects of Chinese Herbal Compounds against Hepatocellular Carcinoma
Molecules 2016, 21(2), 142; doi:10.3390/molecules21020142
Received: 16 November 2015 / Revised: 13 January 2016 / Accepted: 20 January 2016 / Published: 27 January 2016
Cited by 9 | PDF Full-text (482 KB) | HTML Full-text | XML Full-text
Abstract
Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation,
[...] Read more.
Traditional Chinese Medicines, unique biomedical and pharmaceutical resources, have been widely used for hepatocellular carcinoma (HCC) prevention and treatment. Accumulated Chinese herb-derived compounds with significant anti-cancer effects against HCC have been identified. Chinese herbal compounds are effective in preventing carcinogenesis, inhibiting cell proliferation, arresting cell cycle, inducing apoptosis, autophagy, cell senescence and anoikis, inhibiting epithelial-mesenchymal transition, metastasis and angiogenesis, regulating immune function, reversing drug resistance and enhancing the effects of chemotherapy in HCC. This paper comprehensively reviews these compounds and their effects on HCC. Finally, the perspectives and rational application of herbal compounds for HCC management are discussed. Full article
(This article belongs to the Section Natural Products)
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Open AccessReview Chemoinformatics: Achievements and Challenges, a Personal View
Molecules 2016, 21(2), 151; doi:10.3390/molecules21020151
Received: 20 November 2015 / Revised: 14 January 2016 / Accepted: 20 January 2016 / Published: 27 January 2016
Cited by 12 | PDF Full-text (1065 KB) | HTML Full-text | XML Full-text
Abstract
Chemoinformatics provides computer methods for learning from chemical data and for modeling tasks a chemist is facing. The field has evolved in the past 50 years and has substantially shaped how chemical research is performed by providing access to chemical information on a
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Chemoinformatics provides computer methods for learning from chemical data and for modeling tasks a chemist is facing. The field has evolved in the past 50 years and has substantially shaped how chemical research is performed by providing access to chemical information on a scale unattainable by traditional methods. Many physical, chemical and biological data have been predicted from structural data. For the early phases of drug design, methods have been developed that are used in all major pharmaceutical companies. However, all domains of chemistry can benefit from chemoinformatics methods; many areas that are not yet well developed, but could substantially gain from the use of chemoinformatics methods. The quality of data is of crucial importance for successful results. Computer-assisted structure elucidation and computer-assisted synthesis design have been attempted in the early years of chemoinformatics. Because of the importance of these fields to the chemist, new approaches should be made with better hardware and software techniques. Society’s concern about the impact of chemicals on human health and the environment could be met by the development of methods for toxicity prediction and risk assessment. In conjunction with bioinformatics, our understanding of the events in living organisms could be deepened and, thus, novel strategies for curing diseases developed. With so many challenging tasks awaiting solutions, the future is bright for chemoinformatics. Full article
(This article belongs to the Special Issue Chemoinformatics)
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Open AccessReview An Update on the Synthesis of Pyrrolo[1,4]benzodiazepines
Molecules 2016, 21(2), 154; doi:10.3390/molecules21020154
Received: 17 September 2015 / Revised: 23 December 2015 / Accepted: 5 January 2016 / Published: 28 January 2016
Cited by 7 | PDF Full-text (10297 KB) | HTML Full-text | XML Full-text
Abstract
Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered “privileged structures” since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of
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Pyrrolo[1,4]benzodiazepines are tricyclic compounds that are considered “privileged structures” since they possess a wide range of biological activities. The first encounter with these molecules was the isolation of anthramycin from cultures of Streptomyces, followed by determination of the X-ray crystal structure of the molecule and a study of its interaction with DNA. This opened up an intensive synthetic and biological study of the pyrrolo[2,1-c][1,4]benzodiazepines that has culminated in the development of the dimer SJG-136, at present in Phase II clinical trials. The synthetic efforts have brought to light some new synthetic methodology, while the contemporary work is focused on building trimeric pyrrolo[2,1-c][1,4]benzodiazepines linked together by various heterocyclic and aliphatic chains. It is the broad spectrum of biological activities of pyrrolo[1,2-a][1,4]benzodiazepines that has maintained the interest of researchers to date whereas several derivatives of the even less studied pyrrolo[1,2-d][1,4]benzodiazepines were found to be potent non-nucleoside HIV-1 reverse transcriptase inhibitors. The present review is an update on the synthesis of pyrrolo[2,1-c][1,4]benzodiazepines since the last major review of 2011, while the overview of the synthesis of the other two tricyclic isomers is comprehensive. Full article
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Open AccessReview Olive Oil and the Hallmarks of Aging
Molecules 2016, 21(2), 163; doi:10.3390/molecules21020163
Received: 15 December 2015 / Revised: 20 January 2016 / Accepted: 22 January 2016 / Published: 29 January 2016
Cited by 5 | PDF Full-text (315 KB) | HTML Full-text | XML Full-text
Abstract
Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the “hallmarks of aging”, which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all
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Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the “hallmarks of aging”, which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all these hallmarks are targeted by dietary olive oil, particularly by virgin olive oil, since many of its beneficial effects can be accounted not only for the monounsaturated nature of its predominant fatty acid (oleic acid), but also for the bioactivity of its minor compounds, which can act on cells though both direct and indirect mechanisms due to their ability to modulate gene expression. Among the minor constituents of virgin olive oil, secoiridoids stand out for their capacity to modulate many pathways that are relevant for the aging process. Attenuation of aging-related alterations by olive oil or its minor compounds has been observed in cellular, animal and human models. How olive oil targets the hallmarks of aging could explain the improvement of health, reduced risk of aging-associated diseases, and increased longevity which have been associated with consumption of a typical Mediterranean diet containing this edible oil as the predominant fat source. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
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Open AccessReview Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment
Molecules 2016, 21(2), 169; doi:10.3390/molecules21020169
Received: 30 December 2015 / Revised: 22 January 2016 / Accepted: 26 January 2016 / Published: 30 January 2016
Cited by 25 | PDF Full-text (6835 KB) | HTML Full-text | XML Full-text
Abstract
Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed
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Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
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Open AccessReview Recent Development of Plasmonic Resonance-Based Photocatalysis and Photovoltaics for Solar Utilization
Molecules 2016, 21(2), 180; doi:10.3390/molecules21020180
Received: 30 November 2015 / Revised: 24 January 2016 / Accepted: 27 January 2016 / Published: 2 February 2016
Cited by 9 | PDF Full-text (4231 KB) | HTML Full-text | XML Full-text
Abstract
Increasing utilization of solar energy is an effective strategy to tackle our energy and energy-related environmental issues. Both solar photocatalysis (PC) and solar photovoltaics (PV) have high potential to develop technologies of many practical applications. Substantial research efforts are devoted to enhancing visible
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Increasing utilization of solar energy is an effective strategy to tackle our energy and energy-related environmental issues. Both solar photocatalysis (PC) and solar photovoltaics (PV) have high potential to develop technologies of many practical applications. Substantial research efforts are devoted to enhancing visible light activation of the photoelectrocatalytic reactions by various modifications of nanostructured semiconductors. This review paper emphasizes the recent advancement in material modifications by means of the promising localized surface plasmonic resonance (LSPR) mechanisms. The principles of LSPR and its effects on the photonic efficiency of PV and PC are discussed here. Many research findings reveal the promise of Au and Ag plasmonic nanoparticles (NPs). Continual investigation for increasing the stability of the plasmonic NPs will be fruitful. Full article
Open AccessReview Elicitation, an Effective Strategy for the Biotechnological Production of Bioactive High-Added Value Compounds in Plant Cell Factories
Molecules 2016, 21(2), 182; doi:10.3390/molecules21020182
Received: 14 December 2015 / Revised: 26 January 2016 / Accepted: 28 January 2016 / Published: 3 February 2016
Cited by 30 | PDF Full-text (608 KB) | HTML Full-text | XML Full-text
Abstract
Plant in vitro cultures represent an attractive and cost-effective alternative to classical approaches to plant secondary metabolite (PSM) production (the “Plant Cell Factory” concept). Among other advantages, they constitute the only sustainable and eco-friendly system to obtain complex chemical structures biosynthesized by rare
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Plant in vitro cultures represent an attractive and cost-effective alternative to classical approaches to plant secondary metabolite (PSM) production (the “Plant Cell Factory” concept). Among other advantages, they constitute the only sustainable and eco-friendly system to obtain complex chemical structures biosynthesized by rare or endangered plant species that resist domestication. For successful results, the biotechnological production of PSM requires an optimized system, for which elicitation has proved one of the most effective strategies. In plant cell cultures, an elicitor can be defined as a compound introduced in small concentrations to a living system to promote the biosynthesis of the target metabolite. Traditionally, elicitors have been classified in two types, abiotic or biotic, according to their chemical nature and exogenous or endogenous origin, and notably include yeast extract, methyl jasmonate, salicylic acid, vanadyl sulphate and chitosan. In this review, we summarize the enhancing effects of elicitors on the production of high-added value plant compounds such as taxanes, ginsenosides, aryltetralin lignans and other types of polyphenols, focusing particularly on the use of a new generation of elicitors such as coronatine and cyclodextrins. Full article
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Open AccessReview Room Temperature Ionic Liquids as Green Solvent Alternatives in the Metathesis of Oleochemical Feedstocks
Molecules 2016, 21(2), 184; doi:10.3390/molecules21020184
Received: 30 September 2015 / Accepted: 25 January 2016 / Published: 6 February 2016
Cited by 6 | PDF Full-text (2560 KB) | HTML Full-text | XML Full-text
Abstract
One of the most important areas of green chemistry is the application of environmentally friendly solvents in catalysis and synthesis. Conventional organic solvents pose a threat to the environment due to the volatility, highly flammability, toxicity and carcinogenic properties they exhibit. The recently
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One of the most important areas of green chemistry is the application of environmentally friendly solvents in catalysis and synthesis. Conventional organic solvents pose a threat to the environment due to the volatility, highly flammability, toxicity and carcinogenic properties they exhibit. The recently emerged room temperature ionic liquids (RTILs) are promising green solvent alternatives to the volatile organic solvents due to their ease of reuse, non-volatility, thermal stability and ability to dissolve a variety of organic and organometallic compounds. This review explores the use of RTILs as green solvent media in olefin metathesis for applications in the oleochemical industry. Full article
(This article belongs to the Special Issue Ionic Liquids in Organic Synthesis)
Open AccessFeature PaperReview ROMP Synthesis of Iron-Containing Organometallic Polymers
Molecules 2016, 21(2), 198; doi:10.3390/molecules21020198
Received: 28 December 2015 / Accepted: 2 February 2016 / Published: 6 February 2016
Cited by 10 | PDF Full-text (3394 KB) | HTML Full-text | XML Full-text
Abstract
The paper overviews iron-containing polymers prepared by controlled “living” ring-opening metathesis polymerization (ROMP). Developments in the design and synthesis of this class of organometallic polymers are highlighted, pinpointing methodologies and newest trends in advanced applications of hybrid materials based on polymers functionalized with
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The paper overviews iron-containing polymers prepared by controlled “living” ring-opening metathesis polymerization (ROMP). Developments in the design and synthesis of this class of organometallic polymers are highlighted, pinpointing methodologies and newest trends in advanced applications of hybrid materials based on polymers functionalized with iron motifs. Full article
(This article belongs to the Special Issue Olefin Metathesis)
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Open AccessReview Organic Nanomaterials and Their Applications in the Treatment of Oral Diseases
Molecules 2016, 21(2), 207; doi:10.3390/molecules21020207
Received: 15 December 2015 / Revised: 20 January 2016 / Accepted: 28 January 2016 / Published: 9 February 2016
Cited by 6 | PDF Full-text (670 KB) | HTML Full-text | XML Full-text
Abstract
There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for
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There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for several advantages of using natural or synthetic organic nanostructures in a wide variety of dental fields, from implantology, endodontics, and periodontics, to regenerative dentistry and wound healing. Most of the research is concentrated on nanoforms of chitosan, silk fibroin, synthetic polymers or their combinations, but new nanocomposites are constantly being developed. The present work reviews in detail current research on organic nanoparticles and their potential applications in the dental field. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
Open AccessReview Molecular Mechanisms of Inhibition of Streptococcus Species by Phytochemicals
Molecules 2016, 21(2), 215; doi:10.3390/molecules21020215
Received: 7 January 2016 / Revised: 4 February 2016 / Accepted: 6 February 2016 / Published: 17 February 2016
Cited by 7 | PDF Full-text (981 KB) | HTML Full-text | XML Full-text
Abstract
This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals
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This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i) prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii) inhibition of glycolytic enzymes and pH drop; (iii) reduction of biofilm and plaque formation; and (iv) cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Natural Products)
Open AccessReview Focus on Chirality of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors
Molecules 2016, 21(2), 221; doi:10.3390/molecules21020221
Received: 11 January 2016 / Revised: 4 February 2016 / Accepted: 8 February 2016 / Published: 16 February 2016
Cited by 5 | PDF Full-text (2211 KB) | HTML Full-text | XML Full-text
Abstract
Chiral HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are of great interest since one enantiomer is often more potent than the corresponding counterpart against the HIV-1 wild type (WT) and the HIV-1 drug resistant mutant strains. This review exemplifies the various studies made to
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Chiral HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are of great interest since one enantiomer is often more potent than the corresponding counterpart against the HIV-1 wild type (WT) and the HIV-1 drug resistant mutant strains. This review exemplifies the various studies made to investigate the effect of chirality on the antiretroviral activity of top HIV-1 NNRTI compounds, such as nevirapine (NVP), efavirenz (EFV), alkynyl- and alkenylquinazolinone DuPont compounds (DPC), diarylpyrimidine (DAPY), dihydroalkyloxybenzyloxopyrimidine (DABO), phenethylthiazolylthiourea (PETT), indolylarylsulfone (IAS), arylphosphoindole (API) and trifluoromethylated indole (TFMI) The chiral separation, the enantiosynthesis, along with the biological properties of these HIV-1 NNRTIs, are discussed. Full article
(This article belongs to the Special Issue Chiral Drugs)
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Open AccessReview Molecular Theory of Detonation Initiation: Insight from First Principles Modeling of the Decomposition Mechanisms of Organic Nitro Energetic Materials
Molecules 2016, 21(2), 236; doi:10.3390/molecules21020236
Received: 15 December 2015 / Revised: 5 February 2016 / Accepted: 6 February 2016 / Published: 19 February 2016
Cited by 11 | PDF Full-text (2435 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation
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This review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation initiation theory in a widely agreed upon form. However, recent advances in experimental and theoretical methods allow for a constructive and rigorous approach to design and test the theory or at least some of its fundamental building blocks. In this review, we analyzed a set of select experimental and theoretical articles, which were augmented by our own first principles modeling and simulations, to reveal new trends in energetic materials and to refine known existing correlations between their structures, properties, and functions. Our consideration is intentionally limited to the processes of thermally stimulated chemical reactions at the earliest stage of decomposition of molecules and materials containing defects. Full article
(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Organic Chemistry)
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Open AccessReview The Impact of Melatonin in Research
Molecules 2016, 21(2), 240; doi:10.3390/molecules21020240
Received: 10 January 2016 / Revised: 9 February 2016 / Accepted: 11 February 2016 / Published: 20 February 2016
Cited by 2 | PDF Full-text (1242 KB) | HTML Full-text | XML Full-text
Abstract
Citation indexes represent helpful tools for evaluating the impact of articles on research. The aim of this study was to obtain the top-100 ranking of the most cited papers on melatonin, a relevant neurohormone mainly involved in phase-adjusting the biological clock and with
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Citation indexes represent helpful tools for evaluating the impact of articles on research. The aim of this study was to obtain the top-100 ranking of the most cited papers on melatonin, a relevant neurohormone mainly involved in phase-adjusting the biological clock and with certain sleep-promoting capability. An article search was carried out on the Institute for Scientific Information (ISI) Web of Science platform. Numbers of citations, names of authors, journals and their 2014-impact factor, year of publication, and experimental designs of studies were recorded. The ranking of the 100-most cited articles on melatonin research (up to February 2016) revealed a citation range from 1623 to 310. Narrative reviews/expert opinions were the most frequently cited articles, while the main research topics were oxidative stress, sleep physiology, reproduction, circadian rhythms and melatonin receptors. This study represents the first detailed analysis of the 100 top-cited articles published in the field of melatonin research, showing its impact and relevance in the biomedical field. Full article
Open AccessReview Chemistry and Pharmacology of Citrus sinensis
Molecules 2016, 21(2), 247; doi:10.3390/molecules21020247
Received: 16 December 2015 / Revised: 27 January 2016 / Accepted: 9 February 2016 / Published: 22 February 2016
Cited by 3 | PDF Full-text (3745 KB) | HTML Full-text | XML Full-text
Abstract
Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have
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Presently the search for new drugs from natural resources is of growing interest to the pharmaceutical industry. Natural products have been the source of new drugs since ancient times. Plants are a good source of secondary metabolites which have been found to have beneficial properties. The present study is a review of the chemistry and pharmacology of Citrus sinensis. This review reveals the therapeutic potential of C. sinensis as a source of natural compounds with important activities that are beneficial for human health that could be used to develop new drugs. Full article
(This article belongs to the collection Recent Advances in Flavors and Fragrances)
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Open AccessCorrection Correction: Rzepecka-Stojko, A., et al. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity. Molecules 2015, 20, 21732–21749
Molecules 2016, 21(2), 159; doi:10.3390/molecules21020159
Received: 19 January 2016 / Accepted: 19 January 2016 / Published: 28 January 2016
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Abstract
The authors wish to make the following corrections to this paper: [...] Full article
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