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Molecules, Volume 22, Issue 4 (April 2017)

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Cover Story The figure showed in the cover describes the action of barbatic acid from the lichen Cladia [...] Read more.
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Editorial

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Open AccessEditorial Special Issue: Enzyme Immobilization 2016
Molecules 2017, 22(4), 601; doi:10.3390/molecules22040601
Received: 5 April 2017 / Revised: 6 April 2017 / Accepted: 6 April 2017 / Published: 8 April 2017
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(This article belongs to the Special Issue Enzyme Immobilization 2016)

Research

Jump to: Editorial, Review, Other

Open AccessArticle Assessment of the Anti-Hyperglycaemic, Anti-Inflammatory and Antioxidant Activities of the Methanol Extract of Moringa Oleifera in Diabetes-Induced Nephrotoxic Male Wistar Rats
Molecules 2017, 22(4), 439; doi:10.3390/molecules22040439
Received: 18 November 2016 / Revised: 18 February 2017 / Accepted: 7 March 2017 / Published: 23 March 2017
Cited by 2 | PDF Full-text (1240 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes mellitus is an endocrine disease of multiple aetiologies in insulin secretion. A deficiency in insulin results in hyperglycemia with metabolic disturbances of biomolecules. Moringa oleifera (MO) is endemic in the tropics with a variety of ethnomedicinal importance. The leaf of this plant
[...] Read more.
Diabetes mellitus is an endocrine disease of multiple aetiologies in insulin secretion. A deficiency in insulin results in hyperglycemia with metabolic disturbances of biomolecules. Moringa oleifera (MO) is endemic in the tropics with a variety of ethnomedicinal importance. The leaf of this plant has been reported to possess antioxidant and medicinal properties that may be helpful in the treatment and management of diabetes and its associated complications. Diabetes was induced intraperitoneally in rats by a single dose of streptozotocin (55 mg/kg) and treated with methanolic extract of Moringa oleifera (250 mg/kg b.wt) for six weeks. Forty-eight (48) adult male Wistar strain rats were randomly divided into four groups: normal control (NC), Moringa oleifera treated control rats (NC + MO), diabetic rats (DM) and Moringa oleifera treated diabetic rats (DM + MO). Estimation of antioxidant capacity, total polyphenols, flavonoids and flavonols content of Moringa oleifera extract was performed and serum biochemical markers were evaluated. Antioxidants such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione (GSH) and inflammatory biomarkers were determined in the kidney. Results showed high antioxidant capacities of MO extract and improved serum biochemical markers, whilst lipid peroxidation (MDA) levels were reduced in non-diabetic and diabetic rats after MO treatment when compared to normal control. Subsequent administration of MO led to an increased concentration of serum albumin, globulin and total protein with a decrease in the level of MDA, and improvements in CAT, SOD, GSH, GPx, (tumour necrosis factor-alpha)TNF-α and (interleukin-6)IL-6. MO contains potent phytochemical constituents that offer protective action against diabetic-induced renal damage, reactive oxygen species (ROS) and inflammation and could therefore play a role in reducing diabetic complications, particularly in developing countries such as in Africa where the majority cannot afford orthodox medicine. Full article
(This article belongs to the Special Issue Polyphenols and Cardiovascular Disease)
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Open AccessArticle Determination of Ultra-trace Rhodium in Water Samples by Graphite Furnace Atomic Absorption Spectrometry after Cloud Point Extraction Using 2-(5-Iodo-2-Pyridylazo)-5-Dimethylaminoaniline as a Chelating Agent
Molecules 2017, 22(4), 487; doi:10.3390/molecules22040487
Received: 12 February 2017 / Revised: 13 March 2017 / Accepted: 15 March 2017 / Published: 24 March 2017
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Abstract
A highly sensitive method based on cloud point extraction (CPE) separation/preconcentration and graphite furnace atomic absorption spectrometry (GFAAS) detection has been developed for the determination of ultra-trace amounts of rhodium in water samples. A new reagent, 2-(5-iodo-2-pyridylazo)-5-dimethylaminoaniline (5-I-PADMA), was used as the chelating
[...] Read more.
A highly sensitive method based on cloud point extraction (CPE) separation/preconcentration and graphite furnace atomic absorption spectrometry (GFAAS) detection has been developed for the determination of ultra-trace amounts of rhodium in water samples. A new reagent, 2-(5-iodo-2-pyridylazo)-5-dimethylaminoaniline (5-I-PADMA), was used as the chelating agent and the nonionic surfactant TritonX-114 was chosen as extractant. In a HAc-NaAc buffer solution at pH 5.5, Rh(III) reacts with 5-I-PADMA to form a stable chelate by heating in a boiling water bath for 10 min. Subsequently, the chelate is extracted into the surfactant phase and separated from bulk water. The factors affecting CPE were investigated. Under the optimized conditions, the calibration graph was linear in the range of 0.1–6.0 ng/mL, the detection limit was 0.023 ng/mL for rhodium and relative standard deviation was 3.67% (c = 1.0 ng/mL, n = 11).The method has been applied to the determination of trace rhodium in water samples with satisfactory results Full article
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Open AccessArticle Metabolic Profile of Skimmianine in Rats Determined by Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Tandem Mass Spectrometry
Molecules 2017, 22(4), 489; doi:10.3390/molecules22040489
Received: 25 January 2017 / Revised: 5 March 2017 / Accepted: 15 March 2017 / Published: 23 March 2017
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Abstract
Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite
[...] Read more.
Skimmianine is a furoquinoline alkaloid present mainly in the Rutaceae family. It has been reported to have analgesic, antispastic, sedative, anti-inflammatory, and other pharmacologic activities. Despite its critical pharmacological function, its metabolite profiling is still unclear. In this study, the in vivo metabolite profiling of skimmianine in rats was investigated using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The metabolites were predicted using MetabolitePilotTM software. These predicted metabolites were further analyzed by MS2 spectra, and compared with the detailed fragmentation pathway of the skimmianine standard and literature data. A total of 16 metabolites were identified for the first time in rat plasma, urine, and feces samples after oral administration of skimmianine. Skimmianine underwent extensive Phase I and Phase II metabolism in rats. The Phase I biotransformations of skimmianine consist of epoxidation of olefin on its furan ring (M1) followed by the hydrolysis of the epoxide ring (M4), hydroxylation (M2, M3), O-demethylation (M5-M7), didemethylation (M14–M16). The Phase II biotransformations include glucuronide conjugation (M8–M10) and sulfate conjugation (M11–M13). The epoxidation of 2,3-olefinic bond followed by the hydrolysis of the epoxide ring and O-demethylation were the major metabolic pathways of skimmianine. The results provide key information for understanding the biotransformation processes of skimmianine and the related furoquinoline alkaloids. Full article
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Open AccessArticle Bioassay-Guided Isolation of Anti-Inflammatory Components from the Bulbs of Lilium brownii var. viridulum and Identifying the Underlying Mechanism through Acting on the NF-κB/MAPKs Pathway
Molecules 2017, 22(4), 506; doi:10.3390/molecules22040506
Received: 11 February 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 23 March 2017
Cited by 1 | PDF Full-text (6049 KB) | HTML Full-text | XML Full-text
Abstract
The bulbs of Lilium brownii var. viridulum (LB) are commonly used as both traditional Chinese medicines and popular functional food for many centuries in China. Previous studies reported that the extract of lily bulbs exhibited anti-inflammatory activity both in vivo and in vitro,
[...] Read more.
The bulbs of Lilium brownii var. viridulum (LB) are commonly used as both traditional Chinese medicines and popular functional food for many centuries in China. Previous studies reported that the extract of lily bulbs exhibited anti-inflammatory activity both in vivo and in vitro, but its active components and associated molecular mechanisms remain elusive. In the present study, using bioassay-guided isolation method, two phenylpropenoid acylglycerols, 1-O-feruloyl-2-O-p-coumaroylglycerol (1) and 1,3-O-diferuloylglycerol (2), were obtained and identified from the chloroform fraction of LB. Both compounds 1 and 2 significantly decreased the production of nitrite oxide (NO) in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) values of 9.12 ± 0.72 μM and 12.01 ± 1.07 μM, respectively. They also inhibited the production of prostaglandin E2 (PGE2) and several other pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Furthermore, compounds 1 and 2 downregulated the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). They also inhibited the nuclear translocation of nuclear factor-κB (NF-κB) p65 subunit and suppressed mitogen-activated protein kinases (MAPKs) pathway. Taken these data together, compounds 1 and 2 exhibited anti-inflammatory activities through acting on the NF-κB and MAPKs pathway. This research provides the first evidence on the major bioactive constituents and related molecular mechanisms of LB as an anti-inflammatory agent. Our findings also advanced the understanding of LB as a traditional herbal medicine for the prevention and treatment of inflammation. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation
Molecules 2017, 22(4), 507; doi:10.3390/molecules22040507
Received: 9 February 2017 / Revised: 20 March 2017 / Accepted: 21 March 2017 / Published: 27 March 2017
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Abstract
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, 1H-NMR, 13C-NMR and HR-MS spectroscopies. The synthesized
[...] Read more.
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, 1H-NMR, 13C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds 5m, 5o, 5r, 5t, 5y, 5ab, and 5ad possess a good antifungal profile. Compounds 5w was the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds 5m, 5o, 5r, 5w, 5y, 5ab and 5ad showed that compounds 5w and 5ad were the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level in C. albicans. Compounds 5w and 5d inhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound 5w against C. albicans at cellular level. It was determined that compound 5w has a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Molecularly Imprinted Polymers for Selective Extraction of Oblongifolin C from Garcinia yunnanensis Hu
Molecules 2017, 22(4), 508; doi:10.3390/molecules22040508
Received: 26 January 2017 / Revised: 19 March 2017 / Accepted: 21 March 2017 / Published: 23 March 2017
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Abstract
Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in
[...] Read more.
Molecularly imprinted polymers (MIPs) were synthesized and applied for the selective extraction of oblongifolin C (OC) from fruit extracts of Garcinia yunnanensis Hu. A series of experiments and computational approaches were employed to improve the efficiency of screening for optimal MIP systems in the study. The molar ratio (1:4) was eventually chosen based on the comparison of the binding energy of the complexes between the template (OC) and the functional monomers using density functional theory (DFT) at the RI-PBE-D3-gCP/def2-TZVP level of theory. The binding characterization and the molecular recognition mechanism of MIPs were further explained using the molecular modeling method along with NMR and IR spectra data. The reusability of this approach was demonstrated in over 20 batch rebinding experiments. A mass of 140.5 mg of OC (>95% purity) was obtained from the 5 g extracts, with 2 g of MIPs with the best binding properties, through a gradient elution program from 35% to 70% methanol-water solution. At the same time, another structural analog, 46.5 mg of guttiferone K (GK) (>88% purity), was also obtained by the gradient elution procedure. Our results showed that the structural analogs could be separated from the crude extracts by the molecularly imprinted solid-phase extraction (MISPE) using a gradient elution procedure for the first time. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Nerolidol and Farnesol Inhibit Some Cytochrome P450 Activities but Did Not Affect Other Xenobiotic-Metabolizing Enzymes in Rat and Human Hepatic Subcellular Fractions
Molecules 2017, 22(4), 509; doi:10.3390/molecules22040509
Received: 10 February 2017 / Revised: 15 March 2017 / Accepted: 20 March 2017 / Published: 24 March 2017
Cited by 1 | PDF Full-text (589 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they are principally taken as components of many folk medicines and dietary supplements. The aim of our study was to test
[...] Read more.
Sesquiterpenes, 15-carbon compounds formed from three isoprenoid units, are the main components of plant essential oils. Sesquiterpenes occur in human food, but they are principally taken as components of many folk medicines and dietary supplements. The aim of our study was to test and compare the potential inhibitory effect of acyclic sesquiterpenes, trans-nerolidol, cis-nerolidol and farnesol, on the activities of the main xenobiotic-metabolizing enzymes in rat and human liver in vitro. Rat and human subcellular fractions, relatively specific substrates, corresponding coenzymes and HPLC, spectrophotometric or spectrofluorometric analysis of product formation were used. The results showed significant inhibition of cytochromes P450 (namely CYP1A, CYP2B and CYP3A subfamilies) activities by all tested sesquiterpenes in rat as well as in human hepatic microsomes. On the other hand, all tested sesquiterpenes did not significantly affect the activities of carbonyl-reducing enzymes and conjugation enzymes. The results indicate that acyclic sesquiterpenes might affect CYP1A, CYP2B and CYP3A mediated metabolism of concurrently administered drugs and other xenobiotics. The possible drug–sesquiterpene interactions should be verified in in vivo experiments. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Silane Modified Diopside for Improved Interfacial Adhesion and Bioactivity of Composite Scaffolds
Molecules 2017, 22(4), 511; doi:10.3390/molecules22040511
Received: 14 February 2017 / Revised: 18 March 2017 / Accepted: 21 March 2017 / Published: 23 March 2017
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Abstract
Diopside (DIOP) was introduced into polyetheretherketone/polyglycolicacid (PEEK/PGA) scaffolds fabricated via selective laser sintering to improve bioactivity. The DIOP surface was then modified using a silane coupling agent, 3-glycidoxypropyltrimethoxysilane (KH570), to reinforce interfacial adhesion. The results showed that the tensile properties and thermal stability
[...] Read more.
Diopside (DIOP) was introduced into polyetheretherketone/polyglycolicacid (PEEK/PGA) scaffolds fabricated via selective laser sintering to improve bioactivity. The DIOP surface was then modified using a silane coupling agent, 3-glycidoxypropyltrimethoxysilane (KH570), to reinforce interfacial adhesion. The results showed that the tensile properties and thermal stability of the scaffolds were significantly enhanced. It could be explained that, on the one hand, the hydrophilic group of KH570 formed an organic covalent bond with the hydroxy group on DIOP surface. On the other hand, there existed relatively high compatibility between its hydrophobic group and the biopolymer matrix. Thus, the ameliorated interface interaction led to a homogeneous state of DIOP dispersion in the matrix. More importantly, an in vitro bioactivity study demonstrated that the scaffolds with KH570-modified DIOP (KDIOP) exhibited the capability of forming a layer of apatite. In addition, cell culture experiments revealed that they had good biocompatibility compared to the scaffolds without KDIOP. It indicated that the scaffolds with KDIOP possess potential application in tissue engineering. Full article
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Open AccessArticle Design and Synthesis of Novel Pyrazole-Substituted Different Nitrogenous Heterocyclic Ring Systems as Potential Anti-Inflammatory Agents
Molecules 2017, 22(4), 512; doi:10.3390/molecules22040512
Received: 24 January 2017 / Revised: 1 March 2017 / Accepted: 2 March 2017 / Published: 24 March 2017
Cited by 1 | PDF Full-text (1990 KB) | HTML Full-text | XML Full-text
Abstract
With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for
[...] Read more.
With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for their anti-inflammatory activity using the carrageenan-induced paw edema standard technique and revealed that, compound 6b showed increased potency with % inhibition of edema 85.23 ± 1.92 and 85.78 ± 0.99, respectively, higher than the standard reference drugs indomethacin and celebrex (72.99% and 83.76%). Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Isolation, Characterization and Antiproliferative Activity of New Metabolites from the South African Endemic Red Algal Species Laurencia alfredensis
Molecules 2017, 22(4), 513; doi:10.3390/molecules22040513
Received: 27 February 2017 / Revised: 21 March 2017 / Accepted: 21 March 2017 / Published: 23 March 2017
Cited by 2 | PDF Full-text (1773 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis.
[...] Read more.
The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. A sequence of column chromatography, preparative TLC and normal phase HPLC resulted in the isolation of eleven compounds comprising three labdane-type diterpenes (13), four polyether triterpenes (47), three cholestane-type ecdysteroids (810) and a glycolipid (11). Compounds 13, 58 and 10 have not previously been reported, while compound 9 is reported here for the first time from a natural source and the known compound 11 isolated for the first time from the genus Laurencia. The structural elucidation and the relative configuration assignments of the compounds were accomplished by extensive use of 1D- and 2D-NMR, HR-ESI-MS, UV and IR spectroscopic techniques, while the absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. All compounds were evaluated against the MDA-MB-231 breast and HeLa cervical cancer cell lines. Compound 2 exhibited low micromolar antiproliferative activity (IC50 = 9.3 µM) against the triple negative breast carcinoma and compound 7 was similarly active (IC50 = 8.8 µM) against the cervical cancer cell line. Full article
(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)
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Open AccessArticle Anti-Melanogenic Properties of Greek Plants. A Novel Depigmenting Agent from Morus alba Wood
Molecules 2017, 22(4), 514; doi:10.3390/molecules22040514
Received: 12 February 2017 / Revised: 10 March 2017 / Accepted: 12 March 2017 / Published: 23 March 2017
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Abstract
In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors,
[...] Read more.
In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, especially from natural sources. In this study, we investigated 900 extracts from Greek plants for potential tyrosinase inhibitive properties. Among the five most potent extracts, the methanol extract of Morus alba wood (MAM) demonstrated a significant reduction in intracellular tyrosinase and melanin content in B16F10 melanoma cells. Bioassay-guided isolation led to the acquisition of twelve compounds: oxyresveratrol (1), kuwanon C (2), mulberroside A (3), resorcinol (4), dihydrooxyresveratol (5), trans-dihydromorin (6), 2,4,3′-trihydroxydihydrostilbene (7), kuwanon H (8), 2,4-dihydroxybenzaldehyde (9), morusin (10), moracin M (11) and kuwanon G (12). Among these, 2,4,3′-trihydroxydihydrostilbene (7) is isolated for the first time from Morus alba and constitutes a novel potent tyrosinase inhibitor (IC50 0.8 ± 0.15). We report here for the first time dihydrooxyresveratrol (5) as a potent natural tyrosinase inhibitor (IC50 0.3 ± 0.05). Computational docking analysis indicated the binding modes of six tyrosinase inhibitors with the aminoacids of the active centre of tyrosinase. Finally, we found both MAM extract and compounds 1, 6 and 7 to significantly suppress in vivo melanogenesis during zebrafish embryogenesis. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Phenolic Compounds from the Rhizomes of Smilax china L. and Their Anti-Inflammatory Activity
Molecules 2017, 22(4), 515; doi:10.3390/molecules22040515
Received: 20 February 2017 / Revised: 17 March 2017 / Accepted: 18 March 2017 / Published: 3 April 2017
Cited by 2 | PDF Full-text (736 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new triflavanoid, kandelin B-5 (1), was isolated from the rhizomes of Smilax china L., together with six known phenylpropanoid substituted flavan-3-ols (27), nine flavonoids (816), two stilbenoids (17, 18),
[...] Read more.
A new triflavanoid, kandelin B-5 (1), was isolated from the rhizomes of Smilax china L., together with six known phenylpropanoid substituted flavan-3-ols (27), nine flavonoids (816), two stilbenoids (17, 18), and two other compounds (19, 20). The structure of compound 1 was determined on the basis of 1D, 2D NMR and HR-ESI-MS data, as well as chemical method. Compounds 25, 812, 15, 17, and 19 were evaluated for anti-inflammatory activity. Only compounds 10, 15 and 17 showed slightly IL-1β expression inhibitory activities on LPS induced THP-1 cells, with inhibition rate of 15.8%, 37.3%, and 35.8%, respectively, at concentration of 50 μg/mL. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Synthesis of Novel Saccharin Derivatives
Molecules 2017, 22(4), 516; doi:10.3390/molecules22040516
Received: 3 March 2017 / Revised: 20 March 2017 / Accepted: 20 March 2017 / Published: 23 March 2017
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Abstract
The synthesis of saccharin (1,2-benzisothiazol-3-one-1,1-dioxide) derivatives substituted on the benzene ring has seen limited development despite the longevity of this compound’s use as an artificial sweetener. This type of saccharin derivative would however present attractive properties for the development of new bioactive, drug-like
[...] Read more.
The synthesis of saccharin (1,2-benzisothiazol-3-one-1,1-dioxide) derivatives substituted on the benzene ring has seen limited development despite the longevity of this compound’s use as an artificial sweetener. This type of saccharin derivative would however present attractive properties for the development of new bioactive, drug-like small molecule compounds. Here we report the derivatisation of the benzene ring of saccharin using Cu(I)-catalyzed azide alkyne cycloaddition (CuAAC) to synthesise a diverse library of novel saccharin-1,2,3-triazole conjugates. All library compounds retain the capability for interactions with biomolecules via the unmodified sulfonamide and lactam groups of the parent saccharin core heterocycle. The compounds also encompass alternate orientations of the 1,2,3-triazole heterocycle, thus further adding diversity to the potential hydrogen bonding interactions of these compounds with biomolecules of therapeutic interest. Our findings demonstrate that specifically functionalized derivatives of saccharin may be prepared from either saccharin azide or saccharin alkyne building blocks in high yield using CuAAC. Full article
(This article belongs to the Special Issue Women in Organic Chemistry)
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Open AccessArticle Synthesis and Cytotoxicity of N-Substituted Dibenzo[a,j]xanthene-3,11-dicarboxamide Derivatives
Molecules 2017, 22(4), 517; doi:10.3390/molecules22040517
Received: 22 February 2017 / Revised: 16 March 2017 / Accepted: 21 March 2017 / Published: 23 March 2017
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Abstract
In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by 1H-NMR, HR-MS and IR spectra, in which compounds 6a–h
[...] Read more.
In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by 1H-NMR, HR-MS and IR spectra, in which compounds 6a–h were further identified by 13C-NMR spectra. The in vitro antitumor activity of the synthesized compounds was tested by MTT assay. Most of them displayed strong inhibitory activity on human hepatocellular carcinoma cell lines (SK-HEP-1, HepG2 and SMMC-7721 cells) and acute promyelocytic leukemia NB4 cells. Compounds 6c6e exhibited significant inhibitory activity against NB4 cells with IC50 values of 0.52 μM and 0.76 μM, respectively, much lower than 5.31 μM of the positive control As2O3. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives
Molecules 2017, 22(4), 518; doi:10.3390/molecules22040518
Received: 30 January 2017 / Revised: 9 March 2017 / Accepted: 21 March 2017 / Published: 24 March 2017
Cited by 2 | PDF Full-text (3509 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan
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Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant. The DFT conformational analysis, together with the computation of NMR parameters (coupling constants and chemical shifts) and wavefunction analyses (AIM, NBO), provides a full picture. Thus, for all compounds, the most stabilized structures show the OH groups in a conformation allowing IMHB with O5 and O6, when possible. Furthermore, the combined approach points out the occurrence of various IMHBs and the effect of the chemical modulations on their features. Thus, two-center or three-center IMHB interactions are observed in these compounds, depending on the presence or absence of additional HB acceptors, such as methoxy or fluorine. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)
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Open AccessArticle (R)-(−)-Aloesaponol III 8-Methyl Ether from Eremurus persicus: A Novel Compound against Leishmaniosis
Molecules 2017, 22(4), 519; doi:10.3390/molecules22040519
Received: 15 February 2017 / Revised: 14 March 2017 / Accepted: 20 March 2017 / Published: 24 March 2017
Cited by 1 | PDF Full-text (3045 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Leishmaniosis is a neglected tropical disease which affects several millions of people worldwide. The current drug therapies are expensive and often lack efficacy, mainly due to the development of parasite resistance. Hence, there is an urgent need for new drugs effective against Leishmania
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Leishmaniosis is a neglected tropical disease which affects several millions of people worldwide. The current drug therapies are expensive and often lack efficacy, mainly due to the development of parasite resistance. Hence, there is an urgent need for new drugs effective against Leishmania infections. As a part of our ongoing study on the phytochemical characterization and biological investigation of plants used in the traditional medicine of western and central Asia, in the present study, we focused on Eremurus persicus root extract in order to evaluate its potential in the treatment of leishmaniosis. As a result of our study, aloesaponol III 8-methyl ether (ASME) was isolated for the first time from Eremurus persicus root extract, its chemical structure elucidated by means of IR and NMR experiments and the (R) configuration assigned by optical activity measurements: chiroptical aspects were investigated with vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopies and DFT (density functional theory) quantum mechanical calculations. Concerning biological investigations, our results clearly proved that (R)-ASME inhibits Leishmania infantum promastigotes viability (IC50 73 µg/mL), inducing morphological alterations and mitochondrial potential deregulation. Moreover, it is not toxic on macrophages at the concentration tested, thus representing a promising molecule against Leishmania infections. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessCommunication Revision of the Structure of Acremine P from a Marine-Derived Strain of Acremonium persicinum
Molecules 2017, 22(4), 521; doi:10.3390/molecules22040521
Received: 28 February 2017 / Revised: 23 March 2017 / Accepted: 23 March 2017 / Published: 24 March 2017
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Abstract
The previously published structure of the fungal metabolite acremine P is revised by re-evaluation of chemical shift values and NOESY data, and by DFT calculations. Full article
(This article belongs to the Special Issue Women in Organic Chemistry)
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Open AccessArticle Optimized 4,5-Diarylimidazoles as Potent/Selective Inhibitors of Protein Kinase CK1δ and Their Structural Relation to p38α MAPK
Molecules 2017, 22(4), 522; doi:10.3390/molecules22040522
Received: 31 January 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 24 March 2017
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Abstract
The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer’s disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effective small molecule inhibitors for both therapeutic application and
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The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer’s disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effective small molecule inhibitors for both therapeutic application and basic research. Unfortunately, the design of CK1 isoform-specific compounds has proved to be highly complicated due to the existence of six evolutionarily conserved human CK1 members that possess similar, different, or even opposite physiological and pathophysiological implications. Consequently, only few potent and selective CK1δ inhibitors have been reported so far and structurally divergent approaches are urgently needed in order to establish SAR that might enable complete discrimination of CK1 isoforms and related p38α MAPK. In this study we report on design and characterization of optimized 4,5-diarylimidazoles as highly effective ATP-competitive inhibitors of CK1δ with compounds 11b (IC50 CK1δ = 4 nM, IC50 CK1ε = 25 nM), 12a (IC50 CK1δ = 19 nM, IC50 CK1ε = 227 nM), and 16b (IC50 CK1δ = 8 nM, IC50 CK1ε = 81 nM) being among the most potent CK1δ-targeting agents published to date. Inhibitor compound 11b, displaying potential as a pharmacological tool, has further been profiled over a panel of 321 protein kinases exhibiting high selectivity. Cellular efficacy has been evaluated in human pancreatic cancer cell lines Colo357 (EC50 = 3.5 µM) and Panc89 (EC50 = 1.5 µM). SAR is substantiated by X-ray crystallographic analysis of 16b in CK1δ and 11b in p38α. Full article
(This article belongs to the Special Issue Kinase Inhibitors)
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Open AccessArticle Protective Effect of Bicyclol on Anti-Tuberculosis Drug Induced Liver Injury in Rats
Molecules 2017, 22(4), 524; doi:10.3390/molecules22040524
Received: 9 January 2017 / Revised: 20 March 2017 / Accepted: 20 March 2017 / Published: 7 April 2017
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Abstract
The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral
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The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods. Cytokines expression and CYP2E1 activity were determined by ELISA assay and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. The expressions of hepatic CYP2E1 and hepatocyte growth factor (HGF) were assessed by Western blotting. As a result, bicyclol significantly protected against anti-TB drug-induced liver injury by reducing the elevated serum aminotransferases levels and accumulation of hepatic lipids. Meanwhile, the histopathological changes were also attenuated in rats. The protective effect of bicyclol on anti-TB drug-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the inflammatory cytokines and CYP2E1 expression, up-regulate the expression of HGF, and improve mitochondrial function. Furthermore, administration of bicyclol had no significant effect on the plasma pharmacokinetics of the anti-TB drug in rats. Full article
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Open AccessArticle The Effect and Mechanism of Transdermal Penetration Enhancement of Fu’s Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics
Molecules 2017, 22(4), 525; doi:10.3390/molecules22040525
Received: 15 December 2016 / Revised: 9 March 2017 / Accepted: 22 March 2017 / Published: 27 March 2017
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Abstract
Background: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu’s cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism
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Background: In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu’s cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. Methods: With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC0–t, AUMC0–t), area under the zero and first moment curves from 0 to infinity (AUC0–∞, AUMC0–∞), maximum plasma concentration (Cmax) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. Results: In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with the control group, the indomethacin skin percutaneous rate of the FCT low-intensity group (FCTL) was 35.52%, and the enhancement ratio (ER) at 9 h was 1.76X, roughly equivalent to the penetration enhancing effect of the CPEs and iontophoresis. Secondly, the indomethacin percutaneous ratio of the FCT middle-intensity group (FCTM) and FCT high-intensity group (FCTH) were 47.36% and 54.58%, respectively, while the ERs at 9 h were 3.58X and 8.39X, respectively. Thirdly, pharmacokinetic data showed that in vivo indomethacin percutaneous absorption of the FCT was much higher than that of the control, that of the FCTM was slightly higher than that of the CPE, and that of the FCTM group was significantly higher than all others. Meanwhile, variance analysis indicated that the combination of the FCT penetration enhancement method and the CPE method had beneficial effects in enhancing skin penetration: the significance level of the CPE method was 0.0004, which was lower than 0.001, meaning the difference was markedly significant; the significance level of the FCT was also below 0.0001 and its difference markedly significant. The significance level of factor interaction A × B was lower than 0.0001, indicating that the difference in synergism was markedly significant. Moreover, SEM and TEM images showed that the SC surfaces of Sprague-Dawley rats treated with FCT were damaged, and it was difficult to observe the complete surface structure, with SC pores growing larger and its special “brick structure” becoming looser. This indicated that the barrier function of the skin was broken, thus revealing a potentially major route of skin penetration. Conclusion: FCT, as a new form of transdermal penetration technology, has significant penetration effects with TCM characteristics and is of high clinical value. It is worth promoting its development. Full article
(This article belongs to the Special Issue Transdermal Delivery Systems: Current Landscape and Trends)
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Open AccessFeature PaperArticle Synthesis and Antitumor Activity of New Group 3 Metallocene Complexes
Molecules 2017, 22(4), 526; doi:10.3390/molecules22040526
Received: 25 February 2017 / Revised: 17 March 2017 / Accepted: 22 March 2017 / Published: 28 March 2017
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Abstract
The quest for alternative drugs with respect to the well-known cis-platin and its derivatives, which are still used in more than 50% of the treatment regimens for patients suffering from cancer, is highly needed. In this context, organometallic compounds, which are defined
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The quest for alternative drugs with respect to the well-known cis-platin and its derivatives, which are still used in more than 50% of the treatment regimens for patients suffering from cancer, is highly needed. In this context, organometallic compounds, which are defined as metal complexes containing at least one direct covalent metal-carbon bond, have recently been found to be promising anticancer drug candidates. A series of new metallocene complexes with scandium, yttrium, and neodymium have been prepared and characterized. Some of these compounds show a very interesting anti-proliferative activity in triple negative breast cancer cell line (MDA.MB231) and the non-hormone sensitive prostate cancer cell line (DU145). Moreover, the interaction of some of them with biological membranes, evaluated using liposomes as bio-membrane mimetic model systems, seems to be relevant. The biological activity of these compounds, particularly those based on yttrium, already effective at low concentrations on both cancer cell lines, should be taken into account with regard to new therapeutic approaches in anticancer therapy. Full article
(This article belongs to the Section Organometallic Chemistry)
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Open AccessArticle The Structure–Antioxidant Activity Relationship of Ferulates
Molecules 2017, 22(4), 527; doi:10.3390/molecules22040527
Received: 22 December 2016 / Revised: 22 March 2017 / Accepted: 23 March 2017 / Published: 25 March 2017
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Abstract
The antioxidant activity of ferulic acid (1), iso-ferulic acid (2), coniferyl aldehyde (3), methyl ferulate (4), and ethyl ferulate (5) were investigated using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric-reducing antioxidant power (FRAP) assays
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The antioxidant activity of ferulic acid (1), iso-ferulic acid (2), coniferyl aldehyde (3), methyl ferulate (4), and ethyl ferulate (5) were investigated using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric-reducing antioxidant power (FRAP) assays and autoxidation of triacylglycerols of commercially available sunflower oil (TGSO). The compounds tested for ability to scavenge ABTS radical cations was in the order of ferulic acid > coniferyl aldehyde ≈ iso-ferulic acid > ethyl ferulate ≈ methyl ferulate. The results of the FRAP assay for ferulic acid, iso-ferulic acid, and coniferyl aldehyde were similar to and higher than those of methyl ferulate and ethyl ferulate. In the lipid system, iso-ferulic acid showed weak antioxidant activity. The other ferulates exhibited much stronger, yet similar, activities. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)
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Open AccessArticle Subcritical Fluid Extraction of Chinese Quince Seed: Optimization and Product Characterization
Molecules 2017, 22(4), 528; doi:10.3390/molecules22040528
Received: 1 March 2017 / Revised: 15 March 2017 / Accepted: 22 March 2017 / Published: 25 March 2017
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Abstract
Chinese quince seed (CQS) is an underutilized oil source and a potential source of unsaturated fatty acids and α-tocopherol-rich oil. Subcritical fluid (SCF) extraction is executed at lower pressures and temperatures than the pressures and temperatures used in supercritical fluid extraction. However, no
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Chinese quince seed (CQS) is an underutilized oil source and a potential source of unsaturated fatty acids and α-tocopherol-rich oil. Subcritical fluid (SCF) extraction is executed at lower pressures and temperatures than the pressures and temperatures used in supercritical fluid extraction. However, no studies on the SCF extraction of CQS oil are reported. Therefore, the objective of this study was to evaluate the use of SCF for the extraction of CQS oil and to compare the use of SCF with the classical Soxhlet (CS) and supercritical CO2 (SC-CO2) extraction methods. Response surface methodology (RSM) was used to investigate the extraction conditions: temperature (45–65 °C), time (30–50 min), and solvent/solid ratio (5–15 mL/g). The optimization results showed that the highest yield (27.78%) was obtained at 56.18 °C, 40.20 min, and 12.57 mL/g. The oil extracted by SCF had a higher unsaturated fatty acid content (86.37%–86.75%), higher α-tocopherol content (576.0–847.6 mg/kg), lower acid value (3.97 mg/g), and lower peroxide value (0.02 meq O2/kg) than extractions using CS and SC-CO2 methods. The SCF-defatted meal of oilseed exhibited the highest nitrogen solubility index (49.64%) and protein dispersibility index (50.80%), demonstrating that SCF extraction was a promising and efficient technique as an alternative to CS and SC-CO2 methods, as very mild operating conditions and an eco-friendly solvent can be used in the process with maximum preservation of the quality of the meal. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
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Open AccessArticle New Acorane-Type Sesquiterpene from Acorus calamus L.
Molecules 2017, 22(4), 529; doi:10.3390/molecules22040529
Received: 5 March 2017 / Revised: 21 March 2017 / Accepted: 22 March 2017 / Published: 26 March 2017
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Abstract
A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated
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A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated by spectroscopic methods, and the absolute configurations were determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 are nonisoprenoid sesquiterpenoids, likely biosynthesized from an acorane-type sesquiterpene by oxidative fission of the six- or five-membered ring. Moreover, compounds 1 (10 μM), 2 (5 μM and 10 μM) and 3 (10 μM) showed cell proliferation activity on the SK-N-BE (2) cell line. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Hydrogen Sulphide Production in Healthy and Ulcerated Gastric Mucosa of Rats
Molecules 2017, 22(4), 530; doi:10.3390/molecules22040530
Received: 27 January 2017 / Revised: 13 March 2017 / Accepted: 22 March 2017 / Published: 27 March 2017
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Abstract
Hydrogen sulphide (H2S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H2S strengthens the defence mechanisms of the
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Hydrogen sulphide (H2S) is produced endogenously via two enzymes dependent on pyridoxal phosphate (PLP): cystathionine beta-synthase (CBS, EC 4.2.1.22), cystathionase γ-liase (CTH, EC 4.4.1.1), and a third, 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2). H2S strengthens the defence mechanisms of the gastric mucosal barrier, and plays an important role in gastroprotection, including the increased resistance to damage caused by various irritants and non-steroidal anti-inflammatory drugs. The study was conducted to determine the role of H2S in ulcerated gastric mucosa of rats caused by immobilization in cold water (WRS). The activity and expression of γ-cystathionase, cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and rhodanese was compared with healthy mucosa, together with H2S generation, and cysteine, glutathione, and cystathionine levels. The results showed that the defence mechanism against stress is associated with stimulation of the production of H2S in the tissue and confirmed the observed advantageous effect of H2S on healing of gastric ulcers. In case of animals pretreated with exogenous sources of H2S and NaHS, and some changes observed in the ulcerated gastric mucosa tend to return to values found in the healthy tissue, a finding that is in accordance with the previously determined gastroprotective properties of H2S. The results presented in this paper point to the possible role of rhodanese in H2S production in the gastric mucosa of rats, together with the earlier mentioned three enzymes, which are all active in this tissue. Full article
(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)
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Open AccessArticle Choerosponins A and B, Two New Cytotoxic Bridged-Ring Ketones and the Determination of Their Absolute Configurations
Molecules 2017, 22(4), 531; doi:10.3390/molecules22040531
Received: 2 March 2017 / Revised: 21 March 2017 / Accepted: 23 March 2017 / Published: 27 March 2017
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Abstract
Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A (1) and B (2), and their structures were elucidated by spectroscopic methods; their stereochemistry
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Bioactivity-directed fractionation of antitumor compounds from the stem barks of Choerospondias axillaries (Roxb.) Burtt et Hill (Anacardiaceae) afforded two new cytotoxic bridged-ring ketones, choerosponins A (1) and B (2), and their structures were elucidated by spectroscopic methods; their stereochemistry was determined by NOE difference experiments, CD spectra and the modified Mosher’s method. Compound 1 has a rare dioxatricyclo skeleton. Flow cytometry and SRB methods were employed to evaluate the antitumor activity of the two compounds against tsFT210, HCT-15, HeLa, A2780 and MCF-7 cell lines, and both of them showed strong cytotoxicity. MTT and paper disc methods were also used to evaluate their anti-hypoxia and antibacterial activities, and both of them showed no apparent activities. Full article
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Open AccessArticle Constituents of the Roots of Dichapetalum pallidum and Their Anti-Proliferative Activity
Molecules 2017, 22(4), 532; doi:10.3390/molecules22040532
Received: 27 February 2017 / Revised: 22 March 2017 / Accepted: 23 March 2017 / Published: 27 March 2017
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Abstract
As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A
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As part of our search for bioactive compounds from the Dichapetalaceae, repeated chromatographic purification of the roots of a hitherto unexamined species, Dichapetalum pallidum, led to the isolation of the newly occurring 7-hydroxydichapetalin P (1) and the known dichapetalins A (2) and X (3). Also isolated were the known compounds friedelin-2,3-lactone (4), friedelan-3-one (6), friedelan-3β-ol (7) and pomolic (8), as well as the dipeptide aurantiamide acetate (5). The compounds were characterized by direct interpretation of their IR, 1D NMR and 2D NMR spectral data and by comparison of their physico-chemical data, including their chromatographic profiles, with the literature and authentic samples in our compound library for the genus Dichapetalum. The compounds were assayed for their anti-proliferative activities against the human T-lymphocytic leukemia (Jurkat), acute promyelocytic leukemia (HL-60) and T-lymphoblast-like leukemia (CEM) cell lines. Overall, dichapetalin X showed the strongest (3.14 μM) and broadest cytotoxic activities against all the leukemic cell lines tested, exhibiting even stronger activities than the standard compound, curcumin. Full article
(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)
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Open AccessArticle Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro
Molecules 2017, 22(4), 533; doi:10.3390/molecules22040533
Received: 3 February 2017 / Revised: 18 March 2017 / Accepted: 25 March 2017 / Published: 27 March 2017
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Abstract
Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors.
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Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
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Open AccessArticle Novel Sulfamethoxazole Ureas and Oxalamide as Potential Antimycobacterial Agents
Molecules 2017, 22(4), 535; doi:10.3390/molecules22040535
Received: 2 March 2017 / Revised: 23 March 2017 / Accepted: 24 March 2017 / Published: 28 March 2017
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Abstract
Infections caused by Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM) are considered to be a global health problem; current therapeutic options are limited. Sulfonamides have exhibited a wide range of biological activities including those against mycobacteria. Based on the activity of
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Infections caused by Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM) are considered to be a global health problem; current therapeutic options are limited. Sulfonamides have exhibited a wide range of biological activities including those against mycobacteria. Based on the activity of 4-(3-heptylureido)-N-(5-methylisoxazol-3-yl)benzenesulfonamide against NTM, we designed a series of homologous sulfamethoxazole-based n-alkyl ureas (C1–C12), as well as several related ureas and an oxalamide. Fifteen ureas and one oxalamide were synthesized by five synthetic procedures and characterized. They were screened for their activity against Mtb. and three NTM strains (M. avium, M. kansasii). All of them share antimycobacterial properties with minimum inhibitory concentration (MIC) values starting from 2 µM. The highest activity showed 4,4′-[carbonylbis(azanediyl)]bis[N-(5-methylisoxazol-3-yl)benzenesulfonamide] with MIC of 2–62.5 µM (i.e., 1.07–33.28 µg/mL). Among n-alkyl ureas, methyl group is optimal for the inhibition of both Mtb. and NTM. Generally, longer alkyls led to increased MIC values, heptyl being an exception for NTM. Some of the novel derivatives are superior to parent sulfamethoxazole. Several urea and oxalamide derivatives are promising antimycobacterial agents with low micromolar MIC values. Full article
(This article belongs to the Special Issue Sulfonamides)
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Open AccessArticle 3,4-Dihydroxybenzalactone Suppresses Human Non-Small Cell Lung Carcinoma Cells Metastasis via Suppression of Epithelial to Mesenchymal Transition, ROS-Mediated PI3K/AKT/MAPK/MMP and NFκB Signaling Pathways
Molecules 2017, 22(4), 537; doi:10.3390/molecules22040537
Received: 9 February 2017 / Revised: 17 March 2017 / Accepted: 20 March 2017 / Published: 28 March 2017
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Abstract
3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited
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3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited migratory and invasive abilities of cancer cells at noncytotoxic concentrations. We found DBL suppressed enzymatic activities, protein expression, and RNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. Western blot results showed DBL decreased phosphoinositide 3-kinase (PI3K)/AKT, phosphorylation status of mitogen-activated protein kinases (MAPKs), and focal adhesion kinase (FAK)/paxillin, which correlated with cell migratory ability. DBL also affected epithelial to mesenchymal transition (EMT)-related biomarkers. In addition, DBL enhanced cytoprotective effects through elevated antioxidant enzymes including heme oxygenase 1 (HO-1), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). Moreover, DBL influenced the nuclear translocation of nuclear factor κB (NFκB), nuclear factor erythroid 2-related factor 2 (Nrf2), Snail, and Slug in A549 cells. Taken together, these results suggested that treatment with DBL may act as a potential candidate to inhibit lung cancer metastasis by inhibiting MMP-2 and -9 via affecting PI3K/AKT, MAPKs, FAK/paxillin, EMT/Snail and Slug, Nrf2/antioxidant enzymes, and NFκB signaling pathways. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Determination of Vancomycin in Human Serum by Cyclodextrin-Micellar Electrokinetic Capillary Chromatography (CD-MEKC) and Application for PDAP Patients
Molecules 2017, 22(4), 538; doi:10.3390/molecules22040538
Received: 21 February 2017 / Revised: 18 March 2017 / Accepted: 22 March 2017 / Published: 28 March 2017
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Abstract
A simple and sensitive cyclodextrin-micellar electrokinetic capillary chromatography (CD-MEKC) method with UV detection was developed and validated for the determination of vancomycin (VCM) in serum. The separation was achieved in 14 min at 25 °C with a fused-silica capillary column of 40.2 cm
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A simple and sensitive cyclodextrin-micellar electrokinetic capillary chromatography (CD-MEKC) method with UV detection was developed and validated for the determination of vancomycin (VCM) in serum. The separation was achieved in 14 min at 25 °C with a fused-silica capillary column of 40.2 cm × 75 μm i.d. (effective length 30.2 cm) and a run buffer containing 25 mM borate buffer with 50 mM sodium dodecylsulfonate (SDS) (pH 9.5) and 2% sulfobutyl-β-cyclodextrin (sulfobutyl-β-CD). Under optimal conditions for biological samples, good separations with high efficiency and short analysis time were achieved. Several parameters affecting the drug separation from biological matrices were studied, including buffer types, concentrations, and pHs. The methods were validated over the range of 0.9998–99.98 µg/mL. Calibration curves of VCM also showed good linearity (r2 > 0.999). Intra- and interday precisions (relative standard deviation, RSD) were less than 5.80% and 7.38%, and lower limit of quantification (LLOQ) were lower than 1.0 μg/mL. The mean recoveries ranged between 84.03% and 91.69%. The method was successfully applied for monitoring VCM concentrations in serum of patients with peritoneal dialysis-associated peritonitis (PDAP). The assay should be applicable to pharmacokinetic studies and routine therapeutic drug monitoring of this drug in serum. Full article
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Open AccessArticle Bioactive Constituents Obtained from the Seeds of Lepidium apetalum Willd
Molecules 2017, 22(4), 540; doi:10.3390/molecules22040540
Received: 25 January 2017 / Revised: 24 March 2017 / Accepted: 25 March 2017 / Published: 28 March 2017
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Abstract
Three new compounds, apetalumosides C1 (1), D (2), and 1-thio--d-glucopyranosyl(1→1)-1-thio-α-d-glucopyranoside (3), together with twenty-two known ones (4–25) were obtained from the seeds of Lepidium apetalum Willd. Among the known isolates, 58, 10
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Three new compounds, apetalumosides C1 (1), D (2), and 1-thio--d-glucopyranosyl(1→1)-1-thio-α-d-glucopyranoside (3), together with twenty-two known ones (4–25) were obtained from the seeds of Lepidium apetalum Willd. Among the known isolates, 58, 1013, 1620, and 25 were obtained from the genus for the first time; 4, 14, 15, and 2124 were isolated from the species for the first time. Meanwhile, the NMR data of 16 was first reported here. Their structures were determined by means of chemical and spectroscopic methods. On the other hand, their inhibitory effects on sodium oleate-induced triglyceride (TG) overloading in HepG2 cells were evaluated. As a result, two new compounds (1 and 2), together with known isolates 7–11, 13, 14, 16–18, 20, 21, and 25 possessed significant inhibitory effects in the cells. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Thiazine-2-thiones as Masked 1-Azadienes in Cascade Dimerization Reactions)
Molecules 2017, 22(4), 541; doi:10.3390/molecules22040541
Received: 28 February 2017 / Revised: 24 March 2017 / Accepted: 26 March 2017 / Published: 28 March 2017
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Abstract
We report the unexpected formation of a 1-azadiene dimer from 4,6-diphenyl-3,6-dihydro-2H-1,3-thiazine-2-thiones under prolonged microwave irradiation. In this manner, thiazine-2-thiones act as “masked” 1-azadiene equivalents, which makes them useful synthetic tools to access complex heterocyclic frameworks. We compare this dimerization with earlier
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We report the unexpected formation of a 1-azadiene dimer from 4,6-diphenyl-3,6-dihydro-2H-1,3-thiazine-2-thiones under prolonged microwave irradiation. In this manner, thiazine-2-thiones act as “masked” 1-azadiene equivalents, which makes them useful synthetic tools to access complex heterocyclic frameworks. We compare this dimerization with earlier approaches and elaborate on the observed diastereoselectivity. Full article
(This article belongs to the Special Issue MCRs and Related One-Pot Organic Synthesis)
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Open AccessArticle Bisarylureas Based on 1H-Pyrazolo[3,4-d]pyrimidine Scaffold as Novel Pan-RAF Inhibitors with Potent Anti-Proliferative Activities: Structure-Based Design, Synthesis, Biological Evaluation and Molecular Modelling Studies
Molecules 2017, 22(4), 542; doi:10.3390/molecules22040542
Received: 22 February 2017 / Revised: 24 March 2017 / Accepted: 24 March 2017 / Published: 29 March 2017
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Abstract
RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures
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RAF (Ras activating factor) kinases are important and attractive targets for cancer therapy. With the aim of discovering RAF inhibitors that bind to DFG-out inactive conformation created by the movement of Asp-Phe-Gly (DFG), we conducted structure-based drug design using the X-ray cocrystal structures of BRAF (v-raf murine sarcoma viral oncogene homolog B1), starting from bisarylurea derivative based on 1H-pyrazolo[3,4-d]pyrimidine scaffold 1a. Most of the synthesized compounds showed good to excellent inhibitory activities against BRAFV600E kinase, possessed moderate to potent anti-proliferative activities against four tumor cell lines (A375, HT-29, PC-3 and A549) and good selectivity towards cancer cells rather normal cells (Madin-Darby canine kidney, MDCK). The most promising compound, 1v, exhibited potent inhibitory activity against not only BRAFV600E (half maximal inhibitory concentration, IC50 = 23.6 nM) but also wild-type BRAF (IC50 = 51.5 nM) and C-RAF (IC50 = 8.5 nM), and effective cellular anti-proliferative activities against A375, HT-29, PC-3 and A549 cell lines as well as a very good selectivity profile. Moreover, compound 1v mainly arrested the A375 cell line in the G0/G1 stage, and showed significant suppression of MEK (mitogen-activated protein kinase kinase) phosphorylation in A375 and HT-29 cell lines. Taken together, the optimal compound 1v showed excellent in vitro potency as a pan-RAF inhibitor. In addition, the promise of compound 1v was further confirmed by molecular dynamics simulation and binding free energy calculations. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Rats with S-Allyl Cysteine
Molecules 2017, 22(4), 543; doi:10.3390/molecules22040543
Received: 14 February 2017 / Revised: 20 March 2017 / Accepted: 24 March 2017 / Published: 29 March 2017
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Abstract
Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy
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Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 μg/mg and 28.2 ± 2.1 μg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats’ lungs, SAC also attenuated the increased expression of transforming growth factor-β1 (TGF-β1), a central regulator of myofibroblast recruitment, activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-β1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis. Full article
(This article belongs to the Special Issue The Chemistry of Alliums)
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Open AccessArticle A Specific Peptide with Calcium-Binding Capacity from Defatted Schizochytrium sp. Protein Hydrolysates and the Molecular Properties
Molecules 2017, 22(4), 544; doi:10.3390/molecules22040544
Received: 15 February 2017 / Revised: 19 March 2017 / Accepted: 23 March 2017 / Published: 29 March 2017
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Abstract
Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an
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Marine microorganisms have been proposed as a new kind of protein source. Efforts are needed in order to transform the protein-rich biological wastes left after lipid extraction into value-added bio-products. Thus, the utilization of protein recovered from defatted Schizochytrium sp. by-products presents an opportunity. A specific peptide Tyr-Leu (YL) with calcium-binding capacity was purified from defatted Schizochytrium sp. protein hydrolysates through gel filtration chromatography and RP-HPLC. The calcium-binding activity of YL reached 126.34 ± 3.40 μg/mg. The calcium-binding mechanism was investigated through ultraviolet, fluorescence and infrared spectroscopy. The results showed that calcium ions could form dative bonds with carboxyl oxygen atoms and amino nitrogen atoms as well as the nitrogen and oxygen atoms of amide bonds. YL-Ca exhibited excellent thermal stability and solubility, which was beneficial for its absorption and transport in the basic intestinal tract of the human body. Moreover, the cellular uptake of calcium in Caco-2 cells showed that YL-Ca could enhance calcium uptake efficiency and protect calcium ions against precipitation caused by dietary inhibitors such as tannic acid, oxalate, phytate and metal ions. The findings indicate that the by-product of Schizochytrium sp. is a promising source for making peptide-calcium bio-products as algae-based functional supplements for human beings. Full article
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Open AccessArticle Rapid Determination of 30 Polyphenols in Tongmai Formula, a Combination of Puerariae Lobatae Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Chuanxiong Rhizoma, via Liquid Chromatography-Tandem Mass Spectrometry
Molecules 2017, 22(4), 545; doi:10.3390/molecules22040545
Received: 20 February 2017 / Revised: 19 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and
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Tongmai formula (TMF) is a herbal preparation composed of three traditional Chinese medicinal materials: Puerariae Lobatae Radix (Gegen), Salviae Miltiorrhizae Radix et Rhizoma (Danshen) and Chuanxiong Rhizoma (Chuanxiong). It has been used to treat cardiovascular diseases for decades. To develop a reliable and convenient analytical method for a comprehensive determination of polyphenols in TMF and the ascertainment of their chemical correlations with its herbal components, a method combining high-performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated for rapid determination of 30 polyphenols in TMF and its three herbal components. The chromatographic separation was carried out on a Chromolith Fastgradient RP-18 endcapped 50-2 column using an optimized gradient elution. Statistical analysis of obtained data demonstrated that the method had a desirable linearity, precision, and accuracy, as well as excellent sensitivity. The obtained results indicated that, among the 30 polyphenols in TMF, 22 originated from Gegen, 6 originated from Danshen, and 2 originated from Chuanxiong. The major polyphenols in TMF have been identified as puerarin, mirificin, salvianolic acid B, salvianic acid A, 3’-hydroxypuerarin, 3’-methoxypuerarin, and salvianolic acid A, with a combined contribution of 19.2% of the preparation. The development and validation of this method will greatly facilitate future pharmacological studies of TMF and its herbal components, as well as polyphenols in cardiovascular therapies. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Volatiles Emitted at Different Flowering Stages of Jasminum sambac and Expression of Genes Related to α-Farnesene Biosynthesis
Molecules 2017, 22(4), 546; doi:10.3390/molecules22040546
Received: 3 February 2017 / Revised: 22 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the
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Fresh jasmine flowers have been used to make jasmine teas in China, but there has been no complete information about volatile organic compound emissions in relation to flower developmental stages and no science-based knowledge about which floral stage should be used for the infusion. This study monitored volatile organic compounds emitted from living flowers of Jasminum sambac (L.) Ait. ‘Bifoliatum’ at five developmental stages and also from excised flowers. Among the compounds identified, α-farnesene, linalool, and benzyl acetate were most abundant. Since α-farnesene is synthesized through the Mevalonate pathway, four genes encoding 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), farnesyl pyrophosphate synthase, and terpene synthase were isolated. Their expression patterns in living flowers at the five stages and in excised flowers coincided with the emission patterns of α-farnesene. Application of lovastatin, a HMGR inhibitor, significantly reduced the expression of the genes and greatly decreased the emission of α-farnesene. The sweet scent was diminished from lovastatin-treated flowers as well. These results indicate that α-farnesene is an important compound emitted from jasmine flowers, and its emission patterns suggest that flowers at the opening stage or flower buds 8 h after excision should be used for the infusion of tea leaves. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Metal-Free α-C(sp3)–H Functionalized Oxidative Cyclization of Tertiary N,N-Diaryl Amino Alcohols: Theoretical Approach for Mechanistic Pathway
Molecules 2017, 22(4), 547; doi:10.3390/molecules22040547
Received: 21 February 2017 / Revised: 18 March 2017 / Accepted: 24 March 2017 / Published: 29 March 2017
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Abstract
The mechanistic pathway of TEMPO/I2-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 was investigated. Based on direct empirical experiments, three key intermediates (aminium radical cation 3, α-aminoalkyl radical 4, and iminium 5), four types of reactive species
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The mechanistic pathway of TEMPO/I2-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 was investigated. Based on direct empirical experiments, three key intermediates (aminium radical cation 3, α-aminoalkyl radical 4, and iminium 5), four types of reactive species (radical TEMPO, cationic TEMPO, TEMPO-I, and iodo radical), and three types of pathways ((1) SET/PCET mechanism; (2) HAT/1,6-H transfer mechanism; (3) ionic mechanism) were assumed. Under the assumption, nine free energy diagrams were acquired through density functional theory calculations. From the comparison of solution-phase free energy, some possible mechanisms were excluded, and then the chosen plausible mechanisms were concretized using the more stable intermediate 7. Full article
(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)
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Open AccessArticle Black Tea High-Molecular-Weight Polyphenol-Rich Fraction Promotes Hypertrophy during Functional Overload in Mice
Molecules 2017, 22(4), 548; doi:10.3390/molecules22040548
Received: 16 February 2017 / Revised: 22 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5′ adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation.
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Mitochondria activation factor (MAF) is a high-molecular-weight polyphenol extracted from black tea that stimulates training-induced 5′ adenosine monophosphate-activated protein kinase (AMPK) activation and improves endurance capacity. Originally, MAF was purified from black tea using butanol and acetone, making it unsuitable for food preparation. Hence, we extracted a MAF-rich sample “E80” from black tea, using ethanol and water only. Here, we examined the effects of E80 on resistance training. Eight-week old C57BL/6 mice were fed with a normal diet or a diet containing 0.5% E80 for 4, 7 and 14 days under conditions of functional overload. It was found that E80 administration promoted overload-induced hypertrophy and induced phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt, P70 ribosomal protein S6 kinase (p70S6K), and S6 in the plantaris muscle. Therefore, functional overload and E80 administration accelerated mTOR signaling and increased protein synthesis in the muscle, thereby inducing hypertrophy. Full article
(This article belongs to the Special Issue Polyphenols and Antioxidants–The Chemistry of Tea)
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Open AccessArticle The ‘Molecule of the Month’ Website—An Extraordinary Chemistry Educational Resource Online for over 20 Years
Molecules 2017, 22(4), 549; doi:10.3390/molecules22040549
Received: 21 February 2017 / Revised: 27 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
The Molecule of the Month website (http://www.chm.bris.ac.uk/motm/motm.htm) is an educational resource that is celebrating its 20th anniversary. Here we reflect on its pioneering role in promoting new technology for visualizing and presenting chemical information on the web, as well as its achievements, as
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The Molecule of the Month website (http://www.chm.bris.ac.uk/motm/motm.htm) is an educational resource that is celebrating its 20th anniversary. Here we reflect on its pioneering role in promoting new technology for visualizing and presenting chemical information on the web, as well as its achievements, as a free educational resource, both as a teaching aid and as a multi-user, multi-author learning platform. We discuss the legal aspects of such sites, as well as issues around how to make the content permanent. Finally, we look forward to how such sites may evolve in the future. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Assessment of Lipophilicity Indices Derived from Retention Behavior of Antioxidant Compounds in RP-HPLC
Molecules 2017, 22(4), 550; doi:10.3390/molecules22040550
Received: 27 February 2017 / Revised: 26 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
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Abstract
Reverse phase high pressure liquid chromatography was employed in order to evaluate the lipophilicity of antioxidant compounds from different classes, such as phenolic acids, flavanones, flavanols, flavones, anthocyanins, stilbenes, xantonoids, and proanthocyanidins. The retention time of each compound was measured using five different
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Reverse phase high pressure liquid chromatography was employed in order to evaluate the lipophilicity of antioxidant compounds from different classes, such as phenolic acids, flavanones, flavanols, flavones, anthocyanins, stilbenes, xantonoids, and proanthocyanidins. The retention time of each compound was measured using five different HPLC columns: RP18 (LiChroCART, Purosphere RP-18e), C8 (Zorbax, Eclipse XDBC8), C16-Amide (Discovery RP-Amide C16), CN100 (Saulentechnik, Lichrosphere), and pentafluorophenyl (Phenomenex, Kinetex PFP), and the mobile phase consisted of methanol and water (0.1% formic acid) in different proportions. The measurements were conducted at two different column temperatures, room temperature (22 °C) and, in order to mimic the environment from the human body, 37 °C. Furthermore, principal component analysis (PCA) was used to obtain new lipophilicity indices and holistic lipophilicity charts. Additionally, highly representative depictions of the chromatographic behavior of the investigated compounds and stationary phases at different temperatures were obtained using two new chemometric approaches, namely two-way joining cluster analysis and sum of ranking differences. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Physicochemical Properties of Jatropha Oil-Based Polyol Produced by a Two Steps Method
Molecules 2017, 22(4), 551; doi:10.3390/molecules22040551
Received: 10 February 2017 / Revised: 15 March 2017 / Accepted: 25 March 2017 / Published: 29 March 2017
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Abstract
A low cost, abundant, and renewable vegetable oil source has been gaining increasing attention due to its potential to be chemically modified to polyol and thence to become an alternative replacement for the petroleum-based polyol in polyurethane production. In this study, jatropha oil-based
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A low cost, abundant, and renewable vegetable oil source has been gaining increasing attention due to its potential to be chemically modified to polyol and thence to become an alternative replacement for the petroleum-based polyol in polyurethane production. In this study, jatropha oil-based polyol (JOL) was synthesised from non-edible jatropha oil by a two steps process, namely epoxidation and oxirane ring opening. In the first step, the effect of the reaction temperature, the molar ratio of the oil double bond to formic acid, and the reaction time on the oxirane oxygen content (OOC) of the epoxidised jatropha oil (EJO) were investigated. It was found that 4.3% OOC could be achieved with a molar ratio of 1:0.6, a reaction temperature of 60 °C, and 4 h of reaction. Consequently, a series of polyols with hydroxyl numbers in the range of 138–217 mgKOH/g were produced by oxirane ring opening of EJOs, and the physicochemical and rheological properties were studied. Both the EJOs and the JOLs are liquid and have a number average molecular weight (Mn) in the range of 834 to 1457 g/mol and 1349 to 2129 g/mol, respectively. The JOLs exhibited Newtonian behaviour, with a low viscosity of 430–970 mPas. Finally, the JOL with a hydroxyl number of 161 mgKOH/g was further used to synthesise aqueous polyurethane dispersion, and the urethane formation was successfully monitored by Fourier Transform Infrared (FTIR). Full article
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Open AccessArticle Absorption, Metabolic Stability, and Pharmacokinetics of Ginger Phytochemicals
Molecules 2017, 22(4), 553; doi:10.3390/molecules22040553
Received: 17 December 2016 / Revised: 27 February 2017 / Accepted: 1 March 2017 / Published: 30 March 2017
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Abstract
We have previously demonstrated promising anticancer efficacy of orally-fed whole ginger extract (GE) in preclinical prostate models emphasizing the importance of preservation of the natural “milieu”. Essentially, GE primarily includes active ginger phenolics viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogaol (6S).
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We have previously demonstrated promising anticancer efficacy of orally-fed whole ginger extract (GE) in preclinical prostate models emphasizing the importance of preservation of the natural “milieu”. Essentially, GE primarily includes active ginger phenolics viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogaol (6S). However, the druglikeness properties of active GE phenolics like solubility, stability, and metabolic characteristics are poorly understood. Herein, we determined the physicochemical and biochemical properties of GE phenolics by conducting in vitro assays and mouse pharmacokinetic studies with and without co-administration of ketoconazole (KTZ). GE phenolics showed low to moderate solubility in various pH buffers but were stable in simulated gastric and intestinal fluids, indicating their suitability for oral administration. All GE phenolics were metabolically unstable and showed high intrinsic clearance in mouse, rat, dog, and human liver microsomes. Upon oral administration of 250 mg/kg GE, sub-therapeutic concentrations of GE phenolics were observed. Treatment of plasma samples with β-glucuronidase (βgd) increased the exposure of all GE phenolics by 10 to 700-fold. Co-administration of KTZ with GE increased the exposure of free GE phenolics by 3 to 60-fold. Interestingly, when the same samples were treated with βgd, the exposure of GE phenolics increased by 11 to 60-fold, suggesting inhibition of phase I metabolism by KTZ but little effect on glucuronide conjugation. Correlating the in vitro and in vivo results, it is reasonable to conclude that phase II metabolism seems to be the predominant clearance pathway for GE phenolics. We present evidence that the first-pass metabolism, particularly glucuronide conjugation of GE phenolics, underlies low systemic exposure. Full article
(This article belongs to the Special Issue Cancer Chemoprevention)
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Open AccessArticle Intestinal Transport Characteristics and Metabolism of C-Glucosyl Dihydrochalcone, Aspalathin
Molecules 2017, 22(4), 554; doi:10.3390/molecules22040554
Received: 14 March 2017 / Accepted: 27 March 2017 / Published: 30 March 2017
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Abstract
Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability
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Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1–150 µM had an apparent rate of permeability (Papp) typical of poorly absorbed compounds (1.73 × 10−6 cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1.84 × 10−6 cm/s; efflux ratio: 1.1) were excluded as primary transporters, since the Papp of aspalathin was not affected by the presence of specific inhibitors. The Papp of aspalathin was also not affected by constituents of aspalathin-enriched rooibos extracts, but was affected by high glucose concentration (20.5 mM), which decreased the Papp value to 2.9 × 10−7 cm/s. Aspalathin metabolites (sulphated, glucuronidated and methylated) were found in mouse urine, but not in blood, following an oral dose of 50 mg/kg body weight of the pure compound. Sulphates were the predominant metabolites. These findings suggest that aspalathin is absorbed and metabolised in mice to mostly sulphate conjugates detected in urine. Mechanistically, we showed that aspalathin is not actively transported by the glucose transporters, but presumably passes the monolayer paracellularly. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Zerumbone Alleviates Neuropathic Pain through the Involvement of l-Arginine-Nitric Oxide-cGMP-K+ ATP Channel Pathways in Chronic Constriction Injury in Mice Model
Molecules 2017, 22(4), 555; doi:10.3390/molecules22040555
Received: 1 February 2017 / Revised: 22 March 2017 / Accepted: 28 March 2017 / Published: 30 March 2017
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Abstract
The present study investigates the involvement of the l-arginine-Nitric Oxide-cGMP-K+ ATP pathways responsible for the action of anti-allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of l-arginine-NO-cGMP-K+ was assessed
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The present study investigates the involvement of the l-arginine-Nitric Oxide-cGMP-K+ ATP pathways responsible for the action of anti-allodynic and antihyperalgesic activities of zerumbone in chronic constriction injury (CCI) induced neuropathic pain in mice. The role of l-arginine-NO-cGMP-K+ was assessed by the von Frey and the Randall-Selitto tests. Both allodynia and hyperalgesia assessments were carried out on the 14th day post CCI, 30 min after treatments were given for each respective pathway. Anti-allodynic and antihyperalgesic effects of zerumbone (10 mg/kg, i.p) were significantly reversed by the pre-treatment of l-arginine (10 mg/kg), 1H [1,2,4]Oxadiazole[4,3a]quinoxalin-1-one (ODQ), a soluble guanosyl cyclase blocker (2 mg/kg i.p.) and glibenclamide (ATP-sensitive potassium channel blocker) (10 mg/kg i.p.) (p < 0.05). Taken together, these results indicate that systemic administration of zerumbone produces significant anti-allodynic and antihyperalgesic activities in neuropathic pain in mice possibly due to involvement of the l-arginine-NO-cGMP-PKG-K+ ATP channel pathways in CCI model. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Neoantimycins A and B, Two Unusual Benzamido Nine-Membered Dilactones from Marine-Derived Streptomyces antibioticus H12-15
Molecules 2017, 22(4), 557; doi:10.3390/molecules22040557
Received: 22 February 2017 / Revised: 25 March 2017 / Accepted: 27 March 2017 / Published: 30 March 2017
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Abstract
An actinomycete strain (H12-15) isolated from a sea sediment in a mangrove district was identified as Streptomyces antibioticus on the basis of 16S rDNA gene sequence analysis as well as the investigation of its morphological, physiological, and biochemical characteristics. Two novel benzamido nonacyclic
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An actinomycete strain (H12-15) isolated from a sea sediment in a mangrove district was identified as Streptomyces antibioticus on the basis of 16S rDNA gene sequence analysis as well as the investigation of its morphological, physiological, and biochemical characteristics. Two novel benzamido nonacyclic dilactones, namely neoantimycins A (1) and B (2), together with the known antimycins A1ab (3a,b), A2a (4), and A9 (5), were isolated from the culture broth of this strain. Compounds 1 and 2 are the first natural modified ATNs with an unusual benzamide unit. The structures of these new compounds, including their absolute configuration, were established on the basis of HRMS, NMR spectroscopic data, and quantum chemical ECD calculations. Their cytotoxicities against human breast adenocarcinoma cell line MCF-7, the human glioblastoma cell line SF-268, and the human lung cancer cell line NCI-H460 were also tested. All compounds exhibited mild cytotoxic activity. However, Compounds 1 and 2 showed no activity against C. albicans at the test concentration of 1 mg/mL via paper disc diffusion, while the known antimycins showed obvious antifungal activity. Full article
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Open AccessCommunication Chemical Synthesis and Characterization of an Equinatoxin II(1–85) Analogue
Molecules 2017, 22(4), 559; doi:10.3390/molecules22040559
Received: 10 March 2017 / Revised: 29 March 2017 / Accepted: 29 March 2017 / Published: 30 March 2017
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Abstract
The chemical synthesis of an 85 residue analogue of the pore-forming protein, Equinatoxin II (EqtII), was achieved. Peptide precursors with over 40 residues were assembled by solid phase synthesis. The EqtII(1–46) fragment was modified to the reactive C-terminal thioester and native chemical ligation
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The chemical synthesis of an 85 residue analogue of the pore-forming protein, Equinatoxin II (EqtII), was achieved. Peptide precursors with over 40 residues were assembled by solid phase synthesis. The EqtII(1–46) fragment was modified to the reactive C-terminal thioester and native chemical ligation was performed with the A47C mutated EqtII(47–85) peptide to form the EqtII(1–85) analogue. Circular dichroism spectroscopy indicated that the N-terminal domain of EqtII(1–46) and EqtII(1–85) maintains predominantly an α-helical structure in solution and also in the presence of lipid micelles. This demonstrates the feasibility of assembling the full 179 residue protein EqtII via chemical means. Site-specific isotopic labels could be incorporated for structural studies in membranes by solid-state NMR spectroscopy. Full article
(This article belongs to the Special Issue Women in Organic Chemistry)
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Open AccessArticle Effective Subcritical Butane Extraction of Bifenthrin Residue in Black Tea
Molecules 2017, 22(4), 560; doi:10.3390/molecules22040560
Received: 7 February 2017 / Revised: 27 March 2017 / Accepted: 27 March 2017 / Published: 30 March 2017
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Abstract
As a natural and healthy beverage, tea is widely enjoyed; however, the pesticide residues in tea leaves affect the quality and food safety. To develop a highly selective and efficient method for the facile removal of pesticide residues, the subcritical butane extraction (SBE)
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As a natural and healthy beverage, tea is widely enjoyed; however, the pesticide residues in tea leaves affect the quality and food safety. To develop a highly selective and efficient method for the facile removal of pesticide residues, the subcritical butane extraction (SBE) technique was employed, and three variables involving temperature, time and extraction cycles were studied. The optimum SBE conditions were found to be as follows: extraction temperature 45 °C, extraction time 30 min, number of extraction cycles 1, and in such a condition that the extraction efficiency reached as high as 92%. Further, the catechins, theanine, caffeine and aroma components, which determine the quality of the tea, fluctuated after SBE treatment. Compared with the uncrushed leaves, pesticide residues can more easily be removed from crushed leaves, and the practical extraction efficiency was 97%. These results indicate that SBE is a useful method to efficiently remove the bifenthrin, and as appearance is not relevant in the production process, tea leaves should first be crushed and then extracted in order that residual pesticides are thoroughly removed. Full article
(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)
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Open AccessCommunication Novel Palladium(II) Complexes that Influence Prominin-1/CD133 Expression and Stem Cell Factor Release in Tumor Cells
Molecules 2017, 22(4), 561; doi:10.3390/molecules22040561
Received: 20 February 2017 / Revised: 19 March 2017 / Accepted: 23 March 2017 / Published: 30 March 2017
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Abstract
New Pd(II) complexes of 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. The complexes were tested in vitro on human colon and hepatic carcinoma cell lines, normal hepatic cells and hematopoietic progenitor cells. Biological tests proved that Pd(II) complexes 1 and 2 (containing a curcumin
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New Pd(II) complexes of 1,7-bis(2-methoxyphenyl)hepta-1,6-diene-3,5-dione were synthesized and structurally characterized. The complexes were tested in vitro on human colon and hepatic carcinoma cell lines, normal hepatic cells and hematopoietic progenitor cells. Biological tests proved that Pd(II) complexes 1 and 2 (containing a curcumin derivative) exhibit a strong in vitro antitumor effect against the cells derived from human colorectal carcinoma and the hepatic metastasis of a colorectal carcinoma. Complex 1 has an outstanding inhibitory effect against BRAF-mutant colon carcinoma and hepatocarcinoma cell growth; 1 and 2 are both more active than the free ligand and have the capacity to trigger early apoptotic processes. By flow cytometric measurements, an important decrease of prominin-1 (CD133) molecule expression on tumor cells membrane was identified in cell populations subjected to 1 and 2. Quantitative immune enzymatic assay proved restrictions in stem cell factor (SCF) release by treated tumor cells. Although less cytotoxic, the free ligand inhibits the surface marker CD133 expression in hepatocarcinoma cells, and in HT-29 colon carcinoma. The new synthesized Pd(II) complexes 1 and 2 exhibit an important potential through their selective cytotoxic activity and by targeting the stem-like tumor cell populations, which leads to the tumor growth arrest and prevention of metastasis. Full article
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Open AccessArticle Self-Organized TiO2–MnO2 Nanotube Arrays for Efficient Photocatalytic Degradation of Toluene
Molecules 2017, 22(4), 564; doi:10.3390/molecules22040564
Received: 3 February 2017 / Revised: 27 March 2017 / Accepted: 28 March 2017 / Published: 31 March 2017
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Abstract
Vertically oriented, self-organized TiO2–MnO2 nanotube arrays were successfully obtained by one-step anodic oxidation of Ti–Mn alloys in an ethylene glycol-based electrolyte. The as-prepared samples were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV-Vis absorption, photoluminescence spectroscopy, X-ray
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Vertically oriented, self-organized TiO2–MnO2 nanotube arrays were successfully obtained by one-step anodic oxidation of Ti–Mn alloys in an ethylene glycol-based electrolyte. The as-prepared samples were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), UV-Vis absorption, photoluminescence spectroscopy, X-ray diffraction (XRD), and micro-Raman spectroscopy. The effect of the applied potential (30–50 V), manganese content in the alloy (5–15 wt. %) and water content in the electrolyte (2–10 vol. %) on the morphology and photocatalytic properties was investigated for the first time. The photoactivity was assessed in the toluene removal reaction under visible light, using low-powered LEDs as an irradiation source (λmax = 465 nm). Morphology analysis showed that samples consisted of auto-aligned nanotubes over the surface of the alloy, their dimensions were: diameter = 76–118 nm, length = 1.0–3.4 μm and wall thickness = 8–11 nm. It was found that the increase in the applied potential led to increase the dimensions while the increase in the content of manganese in the alloy brought to shorter nanotubes. Notably, all samples were photoactive under the influence of visible light and the highest degradation achieved after 60 min of irradiation was 43%. The excitation mechanism of TiO2–MnO2 NTs under visible light was presented, pointing out the importance of MnO2 species for the generation of e and h+. Full article
(This article belongs to the Special Issue Photon-involving Purification of Water and Air)
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Open AccessArticle Ergosteryl 2-naphthoate, An Ergosterol Derivative, Exhibits Antidepressant Effects Mediated by the Modification of GABAergic and Glutamatergic Systems
Molecules 2017, 22(4), 565; doi:10.3390/molecules22040565
Received: 20 February 2017 / Revised: 27 March 2017 / Accepted: 27 March 2017 / Published: 31 March 2017
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Abstract
Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In
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Phytosterols are a kind of natural component including sitosterol, campesterol, avenasterol, ergosterol (Er) and others. Their main natural sources are vegetable oils and their processed products, followed by grains, by-products of cereals and nuts, and small amounts of fruits, vegetables and mushrooms. In this study, three new Er monoester derivatives were obtained from the reflux reaction with Er: organic acids (furoic acid, salicylic acid and 2-naphthoic acid), 1-Ethylethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP) in dichloromethane. Their chemical structures were defined by IR and NMR. The present study was also undertaken to investigate the antidepressant-like effects of Er and its derivatives in male adult mice models of depression, and their probable involvement of GABAergic and glutamatergic systems by the forced swim test (FST). The results indicated that Er and its derivatives display antidepressant effects. Moreover, one derivative of Er, ergosteryl 2-naphthoate (ErN), exhibited stronger antidepressant activity in vivo compared to Er. Acute administration of ErN (5 mg/kg, i.p.) and a combination of ErN (0.5 mg/kg, i.p.), reboxetine (2.5 mg/kg, i.p.), and tianeptine (15 mg/kg, i.p.) reduced the immobility time in the FST. Pretreatment with bicuculline (a competitive γ-aminobutyric acid (GABA) antagonist, 4 mg/kg, i.p.) and N-methyl-d-aspartic acid (NMDA, an agonist at the glutamate site, 75 mg/kg, i.p.) effectively reversed the antidepressant-like effect of ErN (5 mg/kg, i.p.). However, prazosin (a α1-adrenoceptor antagonist, 1 mg/kg, i.p.) and haloperidol (a non-selective D2 receptor antagonist, 0.2 mg/kg, i.p.) did not eliminate the reduced immobility time. Altogether, these results indicated that ErN produced antidepressant-like activity, which might be mediated by GABAergic and glutamatergic systems. Full article
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Open AccessArticle Biodegradable Poly(Amino Ester) with Aromatic Backbone as Efficient Nonviral Gene Delivery Vectors
Molecules 2017, 22(4), 566; doi:10.3390/molecules22040566
Received: 4 March 2017 / Revised: 25 March 2017 / Accepted: 28 March 2017 / Published: 31 March 2017
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Abstract
The development of gene delivery vectors with high efficiency and biocompatibility is one of the critical points of gene therapy. Two biodegradable poly(amino ester)s were synthesized via ring-opening polymerization between low molecular weight (LMW) PEI and diepoxide. The molecular weights of poly(amino ester)s
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The development of gene delivery vectors with high efficiency and biocompatibility is one of the critical points of gene therapy. Two biodegradable poly(amino ester)s were synthesized via ring-opening polymerization between low molecular weight (LMW) PEI and diepoxide. The molecular weights of poly(amino ester)s were measured by GPC. Agarose gel retardation assays showed that these materials have good DNA-binding ability and can retard the electrophoretic mobility of plasmid DNA (pDNA) at a weight ratio of 1. The formed polyplexes have proper sizes of around 200 nm and zeta-potential values of about 30–40 mV for cellular uptake. In vitro experiments revealed that polymer P2 gave higher transfection efficiency than PEI 25KDa and Lipofectamine 2000 with less toxicity, especially in 293 cells. Results demonstrate that such a type of degradable poly(amino ester) may serve as a promising non-viral gene vector. Full article
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Open AccessArticle Optimizing Sample Size to Assess the Genetic Diversity in Common Vetch (Vicia sativa L.) Populations Using Start Codon Targeted (SCoT) Markers
Molecules 2017, 22(4), 567; doi:10.3390/molecules22040567
Received: 11 February 2017 / Revised: 28 March 2017 / Accepted: 29 March 2017 / Published: 31 March 2017
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Abstract
Common vetch (Vicia sativa subsp. sativa L.) is a self-pollinating annual forage legume with worldwide importance. Here, we investigate the optimal number of individuals that may represent the genetic diversity of a single population, using Start Codon Targeted (SCoT) markers. Two cultivated
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Common vetch (Vicia sativa subsp. sativa L.) is a self-pollinating annual forage legume with worldwide importance. Here, we investigate the optimal number of individuals that may represent the genetic diversity of a single population, using Start Codon Targeted (SCoT) markers. Two cultivated varieties and two wild accessions were evaluated using five SCoT primers, also testing different sampling sizes: 1, 2, 3, 5, 8, 10, 20, 30, 40, 50, and 60 individuals. The results showed that the number of alleles and the Polymorphism Information Content (PIC) were different among the four accessions. Cluster analysis by Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and STRUCTURE placed the 240 individuals into four distinct clusters. The Expected Heterozygosity (HE) and PIC increased along with an increase in sampling size from 1 to 10 plants but did not change significantly when the sample sizes exceeded 10 individuals. At least 90% of the genetic variation in the four germplasms was represented when the sample size was 10. Finally, we concluded that 10 individuals could effectively represent the genetic diversity of one vetch population based on the SCoT markers. This study provides theoretical support for genetic diversity, cultivar identification, evolution, and marker-assisted selection breeding in common vetch. Full article
(This article belongs to the Section Molecular Diversity)
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Open AccessArticle Barbatic Acid Offers a New Possibility for Control of Biomphalaria Glabrata and Schistosomiasis
Molecules 2017, 22(4), 568; doi:10.3390/molecules22040568
Received: 16 January 2017 / Revised: 24 March 2017 / Accepted: 27 March 2017 / Published: 31 March 2017
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Abstract
This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained
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This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (1H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 µg/mL and molluscicidal effects at 20 and 25 µg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 µg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis. Full article
(This article belongs to the Special Issue Lichens: Chemistry, Ecological and Biological Activities)
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Open AccessArticle Effect of Temperature on Tolbutamide Binding to Glycated Serum Albumin
Molecules 2017, 22(4), 569; doi:10.3390/molecules22040569
Received: 21 February 2017 / Revised: 20 March 2017 / Accepted: 27 March 2017 / Published: 31 March 2017
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Abstract
Glycation process occurs in protein and becomes more pronounced in diabetes when an increased amount of reducing sugar is present in bloodstream. Glycation of protein may cause conformational changes resulting in the alterations of its binding properties even though they occur at a
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Glycation process occurs in protein and becomes more pronounced in diabetes when an increased amount of reducing sugar is present in bloodstream. Glycation of protein may cause conformational changes resulting in the alterations of its binding properties even though they occur at a distance from the binding sites. The changes in protein properties could be related to several pathological consequences such as diabetic and nondiabetic cardiovascular diseases, cataract, renal dysfunction and Alzheimer’s disease. The experiment was designed to test the impact of glycation process on sulfonylurea drug tolbutamide-albumin binding under physiological (T = 309 K) and inflammatory (T = 311 K and T = 313 K) states using fluorescence and UV-VIS spectroscopies. It was found in fluorescence analysis experiments that the modification of serum albumin in tryptophanyl and tyrosyl residues environment may affect the tolbutamide (TB) binding to albumin in subdomain IIA and/or IIIA (Sudlow’s site I and/or II), and also in subdomains IB and IIB. We estimated the binding of tolbutamide to albumin described by a mixed nature of interaction (specific and nonspecific). The association constants Ka (L∙mol−1) for tolbutamide at its high affinity sites on non-glycated albumin were in the range of 1.98–7.88 × 104 L∙mol−1ex = 275 nm), 1.20–1.64 × 104 L∙mol−1ex = 295 nm) and decreased to 1.24–0.42 × 104 L∙mol−1 at λex = 275 nm (T = 309 K and T = 311 K) and increased to 2.79 × 104 L∙mol−1 at λex = 275 nm (T = 313 K) and to 4.43–6.61 × 104 L∙mol−1 at λex = 295 nm due to the glycation process. Temperature dependence suggests the important role of van der Waals forces and hydrogen bonding in hydrophobic interactions between tolbutamide and both glycated and non-glycated albumin. We concluded that the changes in the environment of TB binding of albumin in subdomain IIA and/or IIIA as well as in subdomains IB and IIB influence on therapeutic effect and therefore the studies of the binding of tolbutamide (in diabetes) to transporting protein under glycation that refers to the modification of a protein are of great importance in pharmacology and biochemistry. This information may lead to the development of more effective drug therapy in people with diabetes. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Distal Proton Shuttle Mechanism of Ribosome Catalysed Peptide Bond Formation—A Theoretical Study
Molecules 2017, 22(4), 571; doi:10.3390/molecules22040571
Received: 2 February 2017 / Revised: 17 March 2017 / Accepted: 28 March 2017 / Published: 31 March 2017
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Abstract
In this work, we have investigated a novel distal proton shuttle mechanism of ribosome catalyzed peptide bond formation reaction. The reaction was found to follow a two-step mechanism. A distal water molecule located about 6.1 Å away from the attacking amine plays as
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In this work, we have investigated a novel distal proton shuttle mechanism of ribosome catalyzed peptide bond formation reaction. The reaction was found to follow a two-step mechanism. A distal water molecule located about 6.1 Å away from the attacking amine plays as a proton acceptor and results in a charge-separated intermediate that is stabilized by the N terminus of L27 and the A-site A76 5′-phosphate. The ribose A2451 bridges the proton shuttle pathway, thus plays critical role in the reaction. The calculated 27.64 kcal•mol−1 free energy barrier of the distal proton shuttle mechanism is lower than that of eight-membered ring transition state. The distal proton shuttle mechanism studied in this work can provide new insights into the important biological peptide synthesis process. Full article
(This article belongs to the Special Issue Foldamers: Synthesis and Applications)
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Open AccessArticle Sulfur-Doped Carbon Nitride Polymers for Photocatalytic Degradation of Organic Pollutant and Reduction of Cr(VI)
Molecules 2017, 22(4), 572; doi:10.3390/molecules22040572
Received: 18 February 2017 / Revised: 29 March 2017 / Accepted: 29 March 2017 / Published: 1 April 2017
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Abstract
As a promising conjugated polymer, binary carbon nitride has attracted extensive attention as a metal-free and visible-light-responsive photocatalyst in the area of photon-involving purification of water and air. Herein, we report sulfur-doped polymeric carbon nitride microrods that are synthesized through thermal polymerization based
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As a promising conjugated polymer, binary carbon nitride has attracted extensive attention as a metal-free and visible-light-responsive photocatalyst in the area of photon-involving purification of water and air. Herein, we report sulfur-doped polymeric carbon nitride microrods that are synthesized through thermal polymerization based on trithiocyanuric acid and melamine (TM) supramolecular aggregates. By tuning the polymerization temperature, a series of sulfur-doped carbon nitride microrods are prepared. The degradation of Rhodamine B (RhB) and the reduction of hexavalent chromium Cr(VI) are selected as probe reactions to evaluate the photocatalytic activities. Results show that increasing pyrolysis temperature leads to a large specific surface area, strong visible-light absorption, and accelerated electron-hole separation. Compared to bulk carbon nitride, the highly porous sulfur-doped carbon nitride microrods fabricated at 650 °C exhibit remarkably higher photocatalytic activity for degradation of RhB and reduction of Cr(VI). This work highlights the importance of self-assembly approach and temperature-control strategy in the synthesis of photoactive materials for environmental remediation. Full article
(This article belongs to the Special Issue Photon-involving Purification of Water and Air)
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Open AccessArticle Ugonin M, a Helminthostachys zeylanica Constituent, Prevents LPS-Induced Acute Lung Injury through TLR4-Mediated MAPK and NF-κB Signaling Pathways
Molecules 2017, 22(4), 573; doi:10.3390/molecules22040573
Received: 27 February 2017 / Revised: 28 March 2017 / Accepted: 30 March 2017 / Published: 1 April 2017
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Abstract
Helminthostachys zeylanica (L.) Hook. is plant that has been used in traditional Chinese medicine for centuries for the treatment of inflammation, fever, pneumonia, and various disorders. The aims of the present study are to figure out the possible effectiveness of the component Ugonin
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Helminthostachys zeylanica (L.) Hook. is plant that has been used in traditional Chinese medicine for centuries for the treatment of inflammation, fever, pneumonia, and various disorders. The aims of the present study are to figure out the possible effectiveness of the component Ugonin M, a unique flavonoid isolated from H. zeylanica, and to elucidate the mechanism(s) by which it works in the LPS-induced ALI model. In this study, Ugonin M not only inhibited the production of pro-inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6, as well as infiltrated cellular counts and protein content in the bronchoalveolar lavage fluid (BALF) of lipopolysaccharides (LPS)-induced acute lung injury (ALI) mice, but also ameliorated the severity of pulmonary edemas through the score of a histological examination and the ratio of wet to dry weight of lung. Moreover, Ugonin M was observed to significantly suppress LPS-stimulated protein levels of iNOS and COX-2. In addition, we found that Ugonin M not only obviously suppressed NF-κB and MAPK activation via the degradation of NF-κB and IκB-α as well as ERK and p38MAPK active phosphorylation but also inhibited the protein expression level of TLR4. Further, Ugonin M treatment also suppressed the protein levels of MPO and enhanced the protein expressions of HO-1 and antioxidant enzymes (SOD, GPx, and CAT) in lung tissue of LPS-induced ALI mice. It is anticipated that through our findings, there is strong evidence that Ugonin M may exert a potential effect against LPS-induced ALI mice. Hence, Ugonin M could be one of the major effective components of H. zeylanica in the treatment of inflammatory disorders. Full article
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Open AccessArticle Development of a Novel Electrochemical Sensor for Determination of Matrine in Sophora flavescens
Molecules 2017, 22(4), 575; doi:10.3390/molecules22040575
Received: 5 February 2017 / Revised: 29 March 2017 / Accepted: 30 March 2017 / Published: 1 April 2017
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Abstract
A simple and sensitive electrochemical sensor fabricated with graphene nanosheets (GNs) and a hydroxyapatite (HA) nanocomposite–modified glassy carbon electrode (GCE) was developed for the determination of matrine (MT). The as-prepared electrode (GNs/HA/GCE) was verified to outperform bare a GCE and GNs-modified electrode with
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A simple and sensitive electrochemical sensor fabricated with graphene nanosheets (GNs) and a hydroxyapatite (HA) nanocomposite–modified glassy carbon electrode (GCE) was developed for the determination of matrine (MT). The as-prepared electrode (GNs/HA/GCE) was verified to outperform bare a GCE and GNs-modified electrode with increased oxidation peak currents and the decreased over-potential in the redox process of MT, indicating the great enhancement of electrocatalytic activity toward the oxidation of MT by the composite of GNs and HA. Under the optimized conditions, the oxidation peak currents were related linearly with the concentration of MT, ranging from 2 μM to 3 mM, and the detection limit (S/N = 3) was 1.2 μM. In addition, the proposed electrochemical sensor can be successfully applied in the quantitative determination of MT in Sophora flavescens extract. Full article
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Open AccessArticle The Synthesis of 2-Aminobenzoxazoles Using Reusable Ionic Liquid as a Green Catalyst under Mild Conditions
Molecules 2017, 22(4), 576; doi:10.3390/molecules22040576
Received: 9 March 2017 / Revised: 27 March 2017 / Accepted: 28 March 2017 / Published: 2 April 2017
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Abstract
A facile, green, and efficient method for the direct oxidative amination of benzoxazoles using heterocyclic ionic liquid as catalyst has been developed. The reaction proceeded smoothly at room temperature and gave the desirable 2-aminobenzoxazoles with good to excellent yields (up to 97%). The
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A facile, green, and efficient method for the direct oxidative amination of benzoxazoles using heterocyclic ionic liquid as catalyst has been developed. The reaction proceeded smoothly at room temperature and gave the desirable 2-aminobenzoxazoles with good to excellent yields (up to 97%). The catalyst 1-butylpyridinium iodide can be easily recycled and reused with similar efficacies for at least four cycles. Full article
(This article belongs to the Section Green Chemistry)
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Open AccessArticle Experimental and Theoretical Reduction Potentials of Some Biologically Active ortho-Carbonyl para-Quinones
Molecules 2017, 22(4), 577; doi:10.3390/molecules22040577
Received: 29 January 2017 / Revised: 14 March 2017 / Accepted: 29 March 2017 / Published: 4 April 2017
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Abstract
The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four p-quinones was studied experimentally and theoretically. The
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The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four p-quinones was studied experimentally and theoretically. The first and second one-electron reduction potentials of the quinones were determined using cyclic voltammetry and correlated with those calculated by density functional theory (DFT) using three different functionals, BHandHLYP, M06-2x and PBE0. The differences among the experimental reduction potentials were explained in terms of structural effects on the stabilities of the formed species. DFT calculations accurately reproduced the first one-electron experimental reduction potentials with R2 higher than 0.94. The BHandHLYP functional presented the best fit to the experimental values (R2 = 0.957), followed by M06-2x (R2 = 0.947) and PBE0 (R2 = 0.942). Full article
(This article belongs to the Special Issue Organic Electrochemistry)
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Open AccessArticle Design, Synthesis and Biological Evaluation of 2-(2-Amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides as Antiprotozoal Agents
Molecules 2017, 22(4), 579; doi:10.3390/molecules22040579
Received: 24 January 2017 / Revised: 31 March 2017 / Accepted: 31 March 2017 / Published: 4 April 2017
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Abstract
Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is
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Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1H-benzimidazol-1-yl)-N-arylacetamides 18 as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1–8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds 18 were carried out through reaction of 5(6)-nitro-1H-benzimidazol-2-amine (12) with 2-chlroactemides 10ah, in the presence of K2CO3 and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO2 group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule 1 coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer endo-1,6-NO2 predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites (Giardia intestinalis and Entamoeba histolytica) and a urogenital tract parasite (Trichomonas vaginalis) were tested. Compound 7 showed an IC50 of 3.95 μM and was 7 time more active against G. intestinalis than benznidazole. Compounds 7 and 8 showed 4 times more activity against T. vaginalis compared with benznidazole. Full article
(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)
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Open AccessArticle Growth, Structure, and Photocatalytic Properties of Hierarchical V2O5–TiO2 Nanotube Arrays Obtained from the One-step Anodic Oxidation of Ti–V Alloys
Molecules 2017, 22(4), 580; doi:10.3390/molecules22040580
Received: 29 January 2017 / Revised: 30 March 2017 / Accepted: 1 April 2017 / Published: 5 April 2017
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Abstract
V2O5-TiO2 mixed oxide nanotube (NT) layers were successfully prepared via the one-step anodization of Ti-V alloys. The obtained samples were characterized by scanning electron microscopy (SEM), UV-Vis absorption, photoluminescence spectroscopy, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (DRX), and
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V2O5-TiO2 mixed oxide nanotube (NT) layers were successfully prepared via the one-step anodization of Ti-V alloys. The obtained samples were characterized by scanning electron microscopy (SEM), UV-Vis absorption, photoluminescence spectroscopy, energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (DRX), and micro-Raman spectroscopy. The effect of the applied voltage (30–50 V), vanadium content (5–15 wt %) in the alloy, and water content (2–10 vol %) in an ethylene glycol-based electrolyte was studied systematically to determine their influence on the morphology, and for the first-time, on the photocatalytic properties of these nanomaterials. The morphology of the samples varied from sponge-like to highly-organized nanotubular structures. The vanadium content in the alloy was found to have the highest influence on the morphology and the sample with the lowest vanadium content (5 wt %) exhibited the best auto-alignment and self-organization (length = 1 μm, diameter = 86 nm and wall thickness = 11 nm). Additionally, a probable growth mechanism of V2O5-TiO2 nanotubes (NTs) over the Ti-V alloys was presented. Toluene, in the gas phase, was effectively removed through photodegradation under visible light (LEDs, λmax = 465 nm) in the presence of the modified TiO2 nanostructures. The highest degradation value was 35% after 60 min of irradiation. V2O5 species were ascribed as the main structures responsible for the generation of photoactive e and h+ under Vis light and a possible excitation mechanism was proposed. Full article
(This article belongs to the Special Issue Photon-involving Purification of Water and Air)
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Open AccessArticle Strengthening Triterpene Saponins Biosynthesis by Over-Expression of Farnesyl Pyrophosphate Synthase Gene and RNA Interference of Cycloartenol Synthase Gene in Panax notoginseng Cells
Molecules 2017, 22(4), 581; doi:10.3390/molecules22040581
Received: 21 February 2017 / Revised: 20 March 2017 / Accepted: 30 March 2017 / Published: 5 April 2017
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Abstract
To conform to the multiple regulations of triterpene biosynthesis, the gene encoding farnesyl pyrophosphate synthase (FPS) was transformed into Panax notoginseng (P. notoginseng) cells in which RNA interference (RNAi) of the cycloartenol synthase (CAS) gene had been accomplished. Transgenic cell lines
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To conform to the multiple regulations of triterpene biosynthesis, the gene encoding farnesyl pyrophosphate synthase (FPS) was transformed into Panax notoginseng (P. notoginseng) cells in which RNA interference (RNAi) of the cycloartenol synthase (CAS) gene had been accomplished. Transgenic cell lines showed both higher expression levels of FPS and lower expression levels of CAS compared to the wild-type (WT) cells. In the triterpene and phytosterol analysis, transgenic cell lines provided a higher accumulation of total triterpene saponins, and a lower amount of phytosterols in comparison with the WT cells. Compared with the cells in which RNAi of the CAS gene was achieved, the cells with simultaneously over-expressed FPS and silenced CAS showed higher triterpene contents. These results demonstrate that over-expression of FPS can break the rate-limiting reaction catalyzed by FPS in the triterpene saponins biosynthetic pathway; and inhibition of CAS expression can decrease the synthesis metabolic flux of the phytosterol branch. Thus, more precursors flow in the direction of triterpene synthesis, and ultimately promote the accumulation of P. notoginseng saponins. Meanwhile, silencing and over-expressing key enzyme genes simultaneously is more effective than just manipulating one gene in the regulation of saponin biosynthesis. Full article
(This article belongs to the Special Issue Isoprenoid Biosynthesis)
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Open AccessArticle Discovery and Biological Evaluation of a Series of Pyrrolo[2,3-b]pyrazines as Novel FGFR Inhibitors
Molecules 2017, 22(4), 583; doi:10.3390/molecules22040583
Received: 26 January 2017 / Revised: 31 March 2017 / Accepted: 3 April 2017 / Published: 5 April 2017
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Abstract
Abnormality of fibroblast growth factor receptor (FGFR)-mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need for a new chemotype of FGFR inhibitors, here, we started with a hit structure identified
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Abnormality of fibroblast growth factor receptor (FGFR)-mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need for a new chemotype of FGFR inhibitors, here, we started with a hit structure identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and conducted a chemical optimization. After exploring three parts of the hit compound, we finally discovered a new series of pyrrolo[2,3-b]pyrazine FGFR inhibitors, which contain a novel scaffold and unique molecular shape. We believe that our findings can help others to further develop selective FGFR inhibitors. Full article
(This article belongs to the Special Issue Kinase Inhibitors)
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Open AccessArticle Screening and Analysis of the Marker Components in Ganoderma lucidum by HPLC and HPLC-MSn with the Aid of Chemometrics
Molecules 2017, 22(4), 584; doi:10.3390/molecules22040584
Received: 3 January 2017 / Revised: 26 March 2017 / Accepted: 1 April 2017 / Published: 6 April 2017
Cited by 2 | PDF Full-text (1156 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and
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Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) for the identification and quality control of G. lucidum. Fifteen samples from the Chinese provinces of Hainan, Neimeng, Shangdong, Jilin, Anhui, Henan, Yunnan, Guangxi and Fujian were analyzed by HPLC-PAD and HPLC-MSn. Forty-seven compounds were detected by HPLC, of which forty-two compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. Ganoderic acid B, 3,7,15-trihydroxy-11,23-dioxolanost-8,16-dien-26-oic acid, lucidenic acid A, ganoderic acid G, and 3,7-oxo-12-acetylganoderic acid DM were deemed to be the marker compounds to distinguish the samples with different quality according to both CA and PCA. This study provides helpful chemical information for further research on the anti-tumor activity and mechanism of action of G. lucidum. The results proved that fingerprints combined with chemometrics are a simple, rapid and effective method for the quality control of G. lucidum. Full article
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Open AccessArticle Mechanism of Action of Electrospun Chitosan-Based Nanofibers against Meat Spoilage and Pathogenic Bacteria
Molecules 2017, 22(4), 585; doi:10.3390/molecules22040585
Received: 28 January 2017 / Revised: 27 March 2017 / Accepted: 28 March 2017 / Published: 6 April 2017
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Abstract
This study investigates the antibacterial mechanism of action of electrospun chitosan-based nanofibers (CNFs), against Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus and Listeria innocua, bacteria frequently involved in food contamination and spoilage. CNFs were prepared by electrospinning of chitosan and
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This study investigates the antibacterial mechanism of action of electrospun chitosan-based nanofibers (CNFs), against Escherichia coli, Salmonella enterica serovar Typhimurium, Staphylococcus aureus and Listeria innocua, bacteria frequently involved in food contamination and spoilage. CNFs were prepared by electrospinning of chitosan and poly(ethylene oxide) (PEO) blends. The in vitro antibacterial activity of CNFs was evaluated and the susceptibility/resistance of the selected bacteria toward CNFs was examined. Strain susceptibility was evaluated in terms of bacterial type, cell surface hydrophobicity, and charge density, as well as pathogenicity. The efficiency of CNFs on the preservation and shelf life extension of fresh red meat was also assessed. Our results demonstrate that the antibacterial action of CNFs depends on the protonation of their amino groups, regardless of bacterial type and their mechanism of action was bactericidal rather than bacteriostatic. Results also indicate that bacterial susceptibility was not Gram-dependent but strain-dependent, with non-virulent bacteria showing higher susceptibility at a reduction rate of 99.9%. The susceptibility order was: E. coli > L. innocua > S. aureus > S. Typhimurium. Finally, an extension of one week of the shelf life of fresh meat was successfully achieved. These results are promising and of great utility for the potential use of CNFs as bioactive food packaging materials in the food industry, and more specifically in meat quality preservation. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle Optimization of Ionic Liquid-Assisted Extraction of Biflavonoids from Selaginella doederleinii and Evaluation of Its Antioxidant and Antitumor Activity
Molecules 2017, 22(4), 586; doi:10.3390/molecules22040586
Received: 15 February 2017 / Revised: 20 March 2017 / Accepted: 28 March 2017 / Published: 7 April 2017
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Abstract
As new green solvents, ionic liquids (ILs) have been generally applied in the extraction and separation of natural product. In this study, microwave assisted extraction based on IL (IL-MAE) was firstly employed to extract total biflavonoids from Selaginella doederleinii. Based on single-factor
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As new green solvents, ionic liquids (ILs) have been generally applied in the extraction and separation of natural product. In this study, microwave assisted extraction based on IL (IL-MAE) was firstly employed to extract total biflavonoids from Selaginella doederleinii. Based on single-factor experiment, microwave power (300–700 W), extract time (30–50 min) and extract temperature (40–60 °C) on total bioflavonoids and antioxidant activities of the extracts were further investigated by a Box-Behnken design of response surface methodology (RSM) selecting total bioflavonoids yields and IC50 of radical scavenging as index. Besides antioxidant activity of the extract was evaluated by a 2,2-diphenyl-1-picrylhydarzyl (DPPH) and 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) radical scavenging assay, ferric reducing power assay and chelation of ferrous ions assay, and then anticaner activity was also researched against A549 cell line and 7721 cell line. The results illustrated that three factors and their interactions could be well suited for second-order polynomial models (p < 0.05). Through process parameters, optimization of the extract (460 W, 40 min, and 45 °C) and detection of bioactivity, the yield of total bioflavonoids was 16.83 mg/g and IC50 value was 56.24 μg/mL, respectively, indicating the extract has better anti-oxidation effect and antitumor activity. Furthermore, IL-MAE was the most efficient extracting method compared with MAE and Soxhlet extraction, which could improve extraction efficiency in a shorter time and at a lower temperature. In general, ILs-MAE was first adopted to establish a novel and green extraction process on the yields of total biflavonoids from S. doederleinii. In addition, the extract of containing biflavones showed potent antioxidant and anticancer capacity as a utilized valuable bioactive source for natural medicine. Full article
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Open AccessArticle Fraxin Prevents Chemically Induced Hepatotoxicity by Reducing Oxidative Stress
Molecules 2017, 22(4), 587; doi:10.3390/molecules22040587
Received: 31 January 2017 / Revised: 3 April 2017 / Accepted: 4 April 2017 / Published: 6 April 2017
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Abstract
Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the
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Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a CCl4-induced hepatotoxicity rat model. In the fraxin-treated group, glutathione (GSH) significantly increased, while the malondialdehyde (MDA) in the liver significantly decreased. Fraxin also showed radical-scavenging activity. Furthermore, it significantly reduced the t-BHP-induced cytotoxicity and production of reactive oxygen species (ROS) in Hep G2. Fraxin protected Hep G2 cells through Nrf2 pathway-dependent HO-1 expression. The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system. Full article
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Open AccessArticle Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives
Molecules 2017, 22(4), 588; doi:10.3390/molecules22040588
Received: 30 January 2017 / Revised: 28 March 2017 / Accepted: 4 April 2017 / Published: 6 April 2017
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Abstract
Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study
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Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study was the investigation of the antioxidant activity, cytotoxicity and oxidative transformation of nine chromone derivatives. First, we investigated the radical scavenging activity (ABTS), the oxygen radical absorption capacity (ORAC) and the ferric reducing antioxidant power (FRAP) of the investigated molecules. The cytotoxic effects of the compounds were tested on H9c2 cell cultures by the MTT assay. Each compound showed a significant ORAC value compared to the reference. However, the compound 865 possess significantly higher FRAP and ABTS activity in comparison with the reference and other tested molecules, respectively. Based on these assays, the compound 865 was selected for further analysis. In these experiments, we investigated the oxidative metabolism of the compound in vitro. The molecule was oxidized by the Fenton reaction, artificial porphyrin and electrochemistry; then, the formed products were identified by mass spectrometry. Four possible metabolites were detected. The results revealed the compound 865 to possess good antioxidant properties and to be stable metabolically; hence, it is worth investigating its effects in vivo. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
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Open AccessCommunication Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads
Molecules 2017, 22(4), 590; doi:10.3390/molecules22040590
Received: 1 March 2017 / Revised: 31 March 2017 / Accepted: 3 April 2017 / Published: 7 April 2017
Cited by 2 | PDF Full-text (3368 KB) | HTML Full-text | XML Full-text
Abstract
Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In
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Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle The Effect of Citrus Essential Oils and Their Constituents on Growth of Xanthomonas citri subsp. citri
Molecules 2017, 22(4), 591; doi:10.3390/molecules22040591
Received: 13 January 2017 / Revised: 5 April 2017 / Accepted: 5 April 2017 / Published: 14 April 2017
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Abstract
Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is the most devastating of the citrus diseases worldwide. During our study, we found that Essential oils (EOs) of some citrus cultivars are effective on Xcc. Therefore, it prompted
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Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc), is the most devastating of the citrus diseases worldwide. During our study, we found that Essential oils (EOs) of some citrus cultivars are effective on Xcc. Therefore, it prompted us to determine the plant metabolites responsible for the antibacterial properties. We obtained EOs from some locally cultivated citrus by using a Clevenger apparatus and their major constituents were identified by gas chromatography/mass spectrometry (GC-MS). The effect of Citrus aurantium, C. aurantifolia, Fortunella sp. EOs and their major constituents were evaluated against Xcc-KVXCC1 using a disk diffusion assay. Minimal inhibitory and bactericidal concentration of the EOs and their constituents were determined using the broth microdilution method. C. aurantium, C. aurantifolia Eos, and their major constituents including citral, linalool, citronellal, geraniol, α-terpineol, and linalyl acetate indicated antibacterial effects against Xcc. The C. aurantifolia EO and citral showed the highest antibacterial activity among the tested EOs and constituents with inhibition zones of 15 ± 0.33 mm and 16.67 ± 0.88 mm, respectively. Synergistic effects of the constituents were observed between α-terpineol-citral, citral-citronellal, citral-geraniol, and citronellal-geraniol by using a microdilution checkerboard assay. Transmission electron microscopy revealed that exposure of Xcc cells to citral caused cell wall damage and altered cytoplasmic density. We introduced C. aurantifolia and C. aurantium EOs, and their constituents citral, α-terpineol, citronellal, geraniol, and linalool as possible control agents for CBC. Full article
(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)
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Open AccessArticle Two New Thymol Derivatives from the Roots of Ageratina adenophora
Molecules 2017, 22(4), 592; doi:10.3390/molecules22040592
Received: 9 March 2017 / Revised: 2 April 2017 / Accepted: 4 April 2017 / Published: 8 April 2017
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Abstract
Two new thymol derivatives, 7,9-diisobutyryloxy-8-ethoxythymol (1) and 7-acetoxy-8-methoxy-9-isobutyryloxythymol (2), were isolated from fresh roots of Ageratina adenophora, together with four known compounds, 7,9-di-isobutyryloxy-8-methoxythymol (3), 9-oxoageraphorone (4), (−)-isochaminic acid (5) and (1α,6α)-10-hydroxycar-3-ene-2-one (
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Two new thymol derivatives, 7,9-diisobutyryloxy-8-ethoxythymol (1) and 7-acetoxy-8-methoxy-9-isobutyryloxythymol (2), were isolated from fresh roots of Ageratina adenophora, together with four known compounds, 7,9-di-isobutyryloxy-8-methoxythymol (3), 9-oxoageraphorone (4), (−)-isochaminic acid (5) and (1α,6α)-10-hydroxycar-3-ene-2-one (6). Their structures were established on the basis of detailed spectroscopic analysis, and they were all isolated from the roots of A. adenophora for the first time. All the compounds were tested for their in vitro antibacterial activity toward three Gram-positive and two Gram-negative bacterial strains. Thymol derivatives 13 only selectively showed slight in vitro bacteriostatic activity toward three Gram-positive bacteria. The two known carene-type monoterpenes 5 and 6 were found to show moderate in vitro antibacterial activity against all five tested bacterial strains, with MIC values from 15.6 to 62.5 μg/mL. In addition, compounds 5 and 6 were further revealed to show in vitro cytotoxicity against human tumor A549, HeLa and HepG2 cell lines, with IC50 values ranging from 18.36 to 41.87 μM. However, their cytotoxic activities were inferior to those of reference compound adriamycin. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle A Study about Regioisomeric Hydroquinones with Multiple Intramolecular Hydrogen Bonding
Molecules 2017, 22(4), 593; doi:10.3390/molecules22040593
Received: 20 February 2017 / Revised: 27 March 2017 / Accepted: 4 April 2017 / Published: 7 April 2017
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Abstract
A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl
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A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl group and an ortho-carbonyl group (forming a six-membered ring); (b) between the oxygen atom of a phenolic hydroxyl group and the proton of an hydroxyalkyl group (seven membered ring); (c) between the proton of a phenolic hydroxyl group with the oxygen atom of the hydroxyl group of a hydroxyalkyl moiety (seven-membered ring); and (d) between the proton of a phenolic hydroxyl group and an oxygen atom directly bonded to the aromatic ring in ortho position (five-membered ring). A conformational analysis for the rotation around the hydroxyalkyl substituent is also performed. It is observed that there is a correspondence between the conformational energies and the IHB. The strongest intramolecular hydrogen bonds are those involving a phenolic proton and a carbonyl oxygen atom, forming a six-membered ring, and the weakest are those involving a phenolic proton with the oxygen atom of the chromenone, forming five-membered rings. Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules. Full article
(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)
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Open AccessArticle TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells
Molecules 2017, 22(4), 595; doi:10.3390/molecules22040595
Received: 13 March 2017 / Revised: 31 March 2017 / Accepted: 6 April 2017 / Published: 7 April 2017
PDF Full-text (4560 KB) | HTML Full-text | XML Full-text
Abstract
Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells.
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Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. The results revealed that olaquindox treatment reduced the cell viability of HEK293 cells and downregulated the expression of TSC2 in a dose- and time-dependent manner. Meanwhile, olaquindox treatment markedly induced the production of reactive oxygen species (ROS), cascaded to autophagy, oxidative stress, and apoptotic cell death, which was effectively eliminated by the antioxidant N-acetylcysteine (NAC). Furthermore, overexpression of TSC2 attenuated olaquindox-induced autophagy in contrast to inducing the production of ROS, oxidative stress and apoptosis. Consistently, knockdown of TSC2 upregulated autophagy, and decreased olaquindox-induced cell apoptosis. In conclusion, our findings indicate that TSC2 partly participates in olaquindox-induced autophagy, oxidative stress and apoptosis, and demonstrate that TSC2 has a negative regulation role in olaquindox-induced autophagy in HEK293 cells. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
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Open AccessFeature PaperArticle Anti-Trypanosomatid Elemanolide Sesquiterpene Lactones from Vernonia lasiopus O. Hoffm
Molecules 2017, 22(4), 597; doi:10.3390/molecules22040597
Received: 29 March 2017 / Revised: 6 April 2017 / Accepted: 6 April 2017 / Published: 8 April 2017
PDF Full-text (383 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples’ lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid “protozoan” parasite Trypanosoma brucei.
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Sleeping sickness or human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) threatening millions of peoples’ lives with thousands infected. The disease is endemic in poorly developed regions of sub-Saharan Africa and is caused by the kinetoplastid “protozoan” parasite Trypanosoma brucei. The parasites are transmitted to humans through bites of infected tsetse flies of the genus Glossina. The few available drugs for treatment of this disease are highly toxic, difficult to administer, costly and unavailable to poor rural communities bearing the major burden of this infection. Therefore, the search for new efficacious, safe and affordable drugs is of high importance. Vernonia lasiopus O. Hoffm., an indigenous African plant of the Asteraceae family, has been extensively reported to be used ethno-medicinally as a treatment for malaria. Its crude extracts obtained with solvents of different polarity were screened in vitro for anti-protozoal activity and the dichloromethane extract was found to be particularly active against Trypanosoma brucei rhodesiense (IC50 = 0.17 µg/mL). Bioassay-guided chromatographic fractionation of the dichloromethane extract led to the isolation and identification of six elemanolide type sesquiterpene lactones: 8-desacylvernolide, vernolepin, vernomenin, vernodalol, vernodalin and 11,13-dihydrovernodalin. All these elemanolide sesquiterpene lactones showed in vitro anti-trypanosomal activity. They were also tested for cytotoxicity against mammalian cells (L6 cell line). Vernolepin, the main component in the extract, was also the most potent with an IC50 value of 0.05 µg/mL against T.b. rhodesiense trypomastigotes. This compound showed a selectivity index of 14.5, which makes it an interesting candidate for in vivo tests and determination of its mechanism of action. Full article
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Open AccessArticle Acute Hypoglycemic and Antidiabetic Effect of Teuhetenone A Isolated from Turnera diffusa
Molecules 2017, 22(4), 599; doi:10.3390/molecules22040599
Received: 10 February 2017 / Revised: 28 March 2017 / Accepted: 29 March 2017 / Published: 8 April 2017
Cited by 1 | PDF Full-text (1487 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. Turnera diffusa (damiana) is a shrub that grows throughout Mexico and is traditionally used for many illnesses including diabetes. Although a large number of plant
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Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. Turnera diffusa (damiana) is a shrub that grows throughout Mexico and is traditionally used for many illnesses including diabetes. Although a large number of plant metabolites are known, there are no reports indicating which of these are responsible for this activity, and this identification was the objective of the present work. Through bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, teuhetenone A was isolated and identified as the main metabolite responsible for the plant’s hypoglycemic activity. Alpha-glucosidase inhibitory activity and cytotoxicity of this metabolite were determined. Hypoglycemic and antidiabetic activities were evaluated in a murine model of diabetes in vivo, by monitoring glucose levels for six hours and comparing them with levels after administering various controls. Teuhetenone A was not cytotoxic at the tested concentrations, and did not show inhibitory activity in the glucosidase test, and the in vivo assays showed a gradual reduction in glucose levels in normoglycemic and diabetic mice. Considering these results, we suggest that teuhetenone A has potential as an antidiabetic compound, which could be further submitted to preclinical assays. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Screening, Purification and Characterization of Anionic Antimicrobial Proteins from Foeniculum Vulgare
Molecules 2017, 22(4), 602; doi:10.3390/molecules22040602
Received: 2 March 2017 / Revised: 5 April 2017 / Accepted: 6 April 2017 / Published: 8 April 2017
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Abstract
Foeniculum vulgare Mill., commonly called fennel, is a medicinal plant belonging to the Umbelliferae (Apiaceae) family, and is used in traditional medicine. Antibacterial peptides were isolated using sodium phosphate citrate buffer and, for extraction, cetyltrimethyl ammonium bromide (CTAB) buffer with pH 6, have
[...] Read more.
Foeniculum vulgare Mill., commonly called fennel, is a medicinal plant belonging to the Umbelliferae (Apiaceae) family, and is used in traditional medicine. Antibacterial peptides were isolated using sodium phosphate citrate buffer and, for extraction, cetyltrimethyl ammonium bromide (CTAB) buffer with pH 6, have been employed and antimicrobial activity tested against four reference strains. The extracted protein was subjected to 3 kDa dialysis and separation was carried out by DEAE-ion exchange chromatography and further proteins were identified by 2D gel electrophoresis. The results of Foeniculum vulgare elutes obtained from DEAE-ion exchange chromatography were tested for antibacterial activity. Elute 3 shows the highest antibacterial activity on Pseudomonas aeruginosa with a diameter of a zone of inhibition of 16 mm and IC50 value 25.02 (mcg/mL). Based on the findings of the wide usage in treatment of various ailments and day-to-day life, Foeniculum vulgare seeds were used in the present research and have shown promising antibacterial effects, which requires further proteomic research to authenticate the role of the anticipated proteins. Full article
(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)
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Open AccessFeature PaperArticle Gold Nanoparticles Deposited on Surface Modified Carbon Xerogels as Reusable Catalysts for Cyclohexane C-H Activation in the Presence of CO and Water
Molecules 2017, 22(4), 603; doi:10.3390/molecules22040603
Received: 12 February 2017 / Revised: 31 March 2017 / Accepted: 3 April 2017 / Published: 9 April 2017
Cited by 1 | PDF Full-text (3225 KB) | HTML Full-text | XML Full-text
Abstract
The use of gold as a promotor of alkane hydrocarboxylation is reported for the first time. Cyclohexane hydrocarboxylation to cyclohexanecarboxylic acid (up to 55% yield) with CO, water, and peroxodisulfate in a water/acetonitrile medium at circa 50 °C has been achieved in the
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The use of gold as a promotor of alkane hydrocarboxylation is reported for the first time. Cyclohexane hydrocarboxylation to cyclohexanecarboxylic acid (up to 55% yield) with CO, water, and peroxodisulfate in a water/acetonitrile medium at circa 50 °C has been achieved in the presence of gold nanoparticles deposited by a colloidal method on a carbon xerogel in its original form (CX), after oxidation with HNO3 (-ox), or after oxidation with HNO3 and subsequent treatment with NaOH (-ox-Na). Au/CX-ox-Na behaves as re-usable catalyst maintaining its initial activity and selectivity for at least seven consecutive cycles. Green metric values of atom economy or carbon efficiency also attest to the improvement brought by this novel catalytic system to the hydrocarboxylation of cyclohexane. Full article
(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)
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Open AccessArticle Structural Characterization and Antifungal Studies of Zinc-Doped Hydroxyapatite Coatings
Molecules 2017, 22(4), 604; doi:10.3390/molecules22040604
Received: 6 March 2017 / Revised: 31 March 2017 / Accepted: 7 April 2017 / Published: 9 April 2017
Cited by 2 | PDF Full-text (16915 KB) | HTML Full-text | XML Full-text
Abstract
The present study is focused on the synthesis, characterization and antifungal evaluation of zinc-doped hydroxyapatite (Zn:HAp) coatings. The Zn:HAp coatings were deposited on a pure Si (Zn:HAp_Si) and Ti (Zn:HAp_Ti) substrate by a sol-gel dip coating method using a zinc-doped hydroxyapatite nanogel. The
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The present study is focused on the synthesis, characterization and antifungal evaluation of zinc-doped hydroxyapatite (Zn:HAp) coatings. The Zn:HAp coatings were deposited on a pure Si (Zn:HAp_Si) and Ti (Zn:HAp_Ti) substrate by a sol-gel dip coating method using a zinc-doped hydroxyapatite nanogel. The nature of the crystal phase was determined by X-ray diffraction (XRD). The crystalline phase of the prepared Zn:HAp composite was assigned to hexagonal hydroxyapatite in the P63/m space group. The colloidal properties of the resulting Zn:HAp (xZn = 0.1) nanogel were analyzed by Dynamic Light Scattering (DLS) and zeta potential. Scanning Electron Microscopy (SEM) was used to investigate the morphology of the zinc-doped hydroxyapatite (Zn:HAp) nanogel composite and Zn:HAp coatings. The elements Ca, P, O and Zn were found in the Zn:HAp composite. According to the EDX results, the degree of Zn substitution in the structure of Zn:HAp composite was 1.67 wt%. Moreover, the antifungal activity of Zn:HAp_Si and Zn:HAp_Ti against Candida albicans (C. albicans) was evaluated. A decrease in the number of surviving cells was not observed under dark conditions, whereas under daylight and UV light illumination a major decrease in the number of surviving cells was observed. Full article
(This article belongs to the Special Issue Antibacterial Materials and Coatings)
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Open AccessArticle An Efficient One-Pot Protocol for the Synthesis of Substituted 3,4-Dihydropyrimidin-2(1H)-ones Using Metallophthalocyanines (MPcs) as Potent Heterogeneous Catalysts: Synthesis, Characterization, Aggregation and Antimicrobial Activity
Molecules 2017, 22(4), 605; doi:10.3390/molecules22040605
Received: 3 February 2017 / Revised: 15 March 2017 / Accepted: 23 March 2017 / Published: 9 April 2017
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Abstract
In this study, novel phthalonitrile 3 and their corresponding metal-free 4 and metallophthalocyanine derivatives 57 bearing 2-isopropenyl-4-methoxy-1-methylbenzene groups were synthesized and characterized. 3,4-Dihydropyrimidinones have been synthesized by a modified Biginelli-type reaction with various metallophthalocyanines 57 as catalysts. Compared to
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In this study, novel phthalonitrile 3 and their corresponding metal-free 4 and metallophthalocyanine derivatives 57 bearing 2-isopropenyl-4-methoxy-1-methylbenzene groups were synthesized and characterized. 3,4-Dihydropyrimidinones have been synthesized by a modified Biginelli-type reaction with various metallophthalocyanines 57 as catalysts. Compared to the classical Biginielli reaction, the new method has the advantages of good yield and short reaction time. Among the various metallophthalocyanines studied, cobalt (II)-phthalocyanine was found to be most active for this transformation. The newly prepared compounds were characterized using elemental analyses, MS, IR, 1H/13C-NMR and UV-Vis spectroscopy. In addition; the 3,4-dihydropyrimidinones (DHPMs) 812 were investigated for antimicrobial activities and revealed good activity. The minimum inhibitory concentration (MIC) was determined by the microdilution technique in Mueller-Hinton broth. The MICs were recorded after 24 hours of incubation at 37 °C. These results are promising, showing these compounds are biologically active. Full article
(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)
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Open AccessArticle Thermo-Oxidative Stability Evaluation of Bullfrog (Rana catesbeiana Shaw) Oil
Molecules 2017, 22(4), 606; doi:10.3390/molecules22040606
Received: 6 January 2017 / Revised: 2 March 2017 / Accepted: 6 April 2017 / Published: 10 April 2017
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Abstract
Bullfrog oil (BO), a natural product obtained from recycling of adipose tissue from the amphibian Rana catesbeiana Shaw, has been recently evaluated as a therapeutic activity ingredient. This work aimed to evaluate the long-term and accelerated thermal oxidative stabilities of this product, which
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Bullfrog oil (BO), a natural product obtained from recycling of adipose tissue from the amphibian Rana catesbeiana Shaw, has been recently evaluated as a therapeutic activity ingredient. This work aimed to evaluate the long-term and accelerated thermal oxidative stabilities of this product, which is a promising raw material for emulsion technology development. BO was extracted from amphibian adipose tissue at 70 °C with a yield of 60% ± 0.9%. Its main fatty acid compounds were oleic (30.0%) and eicosapentaenoic (17.6%) acids. Using titration techniques, BO showed peroxide, acid, iodine and saponification indices of 1.92 mEq·O2/kg, 2.95 mg·KOH/g oil, 104.2 g I2/100 g oil and 171.2 mg·KOH/g oil, respectively. In order to improve the accelerated oxidative stability of BO, synthetic antioxidants butylhydroxytoluene (BHT) and buthylhydroxyanisole (BHA) were used. The addition of BHT increased the oxidation induction time compared to the pure oil, or the oil containing BHA. From the results, the best oil-antioxidant mixture and concentration to increase the oxidative stability and allow the oil to be a stable raw material for formulation purposes was derived. Full article
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Open AccessArticle Computational Identification of Antibody Epitopes on the Dengue Virus NS1 Protein
Molecules 2017, 22(4), 607; doi:10.3390/molecules22040607
Received: 6 November 2016 / Revised: 5 April 2017 / Accepted: 6 April 2017 / Published: 10 April 2017
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Abstract
We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1–4) that are bound by a small panel
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We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1–4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5.3 were identified, revealing the reasons for the serotype specificity of 1H7.4 and 1G5.3, and the non-selectivity of Gus2. As DENV NS1 is critical for virus replication and a key vaccine candidate, epitope prediction will be valuable in designing appropriate vaccine control strategies. The ability to predict potential epitopes by computational methods significantly reduces the amount of experimental work required to screen peptide libraries for epitope mapping. Full article
(This article belongs to the Special Issue Biomolecular Simulations)
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Open AccessArticle Structure-Activity and Lipophilicity Relationships of Selected Antibacterial Natural Flavones and Flavanones of Chilean Flora
Molecules 2017, 22(4), 608; doi:10.3390/molecules22040608
Received: 7 December 2016 / Revised: 31 March 2017 / Accepted: 5 April 2017 / Published: 10 April 2017
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Abstract
In this study, we tested eight naturally-occurring flavonoids—three flavanones and five flavones—for their possible antibacterial properties against four Gram-positive and four Gram-negative bacteria. Flavonoids are known for their antimicrobial properties, and due their structural diversity; these plant-derived compounds are a good model to
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In this study, we tested eight naturally-occurring flavonoids—three flavanones and five flavones—for their possible antibacterial properties against four Gram-positive and four Gram-negative bacteria. Flavonoids are known for their antimicrobial properties, and due their structural diversity; these plant-derived compounds are a good model to study potential novel antibacterial mechanisms. The lipophilicity and the interaction of antibacterial compounds with the cell membrane define the success or failure to access its target. Therefore, through the determination of partition coefficients in a non-polar/aqueous phase, lipophilicity estimation and the quantification of the antibacterial activity of different flavonoids, flavanones, and flavones, a relationship between these parameters was assessed. Active flavonoids presented diffusion coefficients between 9.4 × 10−10 and 12.3 × 10−10 m2/s and lipophilicity range between 2.0 to 3.3. Active flavonoids against Gram-negative bacteria showed a narrower range of lipophilicity values, compared to active flavonoids against Gram-positive bacteria, which showed a wide range of lipophilicity and cell lysis. Galangin was the most active flavonoid, whose structural features are the presence of two hydroxyl groups located strategically on ring A and the absence of polar groups on ring B. Methylation of one hydroxyl group decreases the activity in 3-O-methylgalangin, and methylation of both hydroxyl groups caused inactivation, as shown for 3,7-O-dimethylgalangin. In conclusion, the amphipathic features of flavonoids play a crucial role in the antibacterial activity. In these compounds, hydrophilic and hydrophobic moieties must be present and could be predicted by lipophilicity analysis. Full article
(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)
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Open AccessArticle Anti-Inflammatory and Antioxidant Properties of Casein Hydrolysate Produced Using High Hydrostatic Pressure Combined with Proteolytic Enzymes
Molecules 2017, 22(4), 609; doi:10.3390/molecules22040609
Received: 9 March 2017 / Revised: 3 April 2017 / Accepted: 6 April 2017 / Published: 10 April 2017
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Abstract
Casein-derived peptides are shown to possess radical scavenging and metal chelating properties. The objective of this study was to evaluate novel anti-inflammatory properties of casein hydrolysates (CH) produced by an eco-friendly process that combines high hydrostatic pressure with enzymatic hydrolysis (HHP-EH). Casein was
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Casein-derived peptides are shown to possess radical scavenging and metal chelating properties. The objective of this study was to evaluate novel anti-inflammatory properties of casein hydrolysates (CH) produced by an eco-friendly process that combines high hydrostatic pressure with enzymatic hydrolysis (HHP-EH). Casein was hydrolysed by different proteases, including flavourzyme (Fla), savinase (Sav), thermolysin (Ther), trypsin (Try), and elastase (Ela) at 0.1, 50, 100, and 200 MPa pressure levels under various enzyme-to-substrate ratios and incubation times. Casein hydrolysates were evaluated for the degree of hydrolysis (DH), molecular weight distribution patterns, and anti-inflammatory properties in chemical and cellular models. Hydrolysates produced using HHP-EH exhibited higher DH values and proportions of smaller peptides compared to atmospheric pressure-enzymatic hydrolysis (AP-EH). Among five enzymes, Fla-digested HHP-EH-CH (HHP-Fla-CH) showed significantly higher antioxidant properties than AP-Fla-CH. The anti-inflammatory properties of HHP-Fla-CH were also observed by significantly reduced nitric oxide and by the suppression of the synthesis of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) revealed that 59% of the amino acids of the peptides in HHP-Fla-CH were composed of proline, valine, and leucine, indicating the potential anti-inflammatory properties. In conclusion, the HHP-EH method provides a promising technology to produce bioactive peptides from casein i