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Molecules, Volume 17, Issue 5 (May 2012), Pages 4770-6178

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Open AccessArticle Synthesis of Potent Inhibitors of β-Ketoacyl-Acyl Carrier Protein Synthase III as Potential Antimicrobial Agents
Molecules 2012, 17(5), 4770-4781; doi:10.3390/molecules17054770
Received: 26 December 2011 / Revised: 11 April 2012 / Accepted: 16 April 2012 / Published: 25 April 2012
Cited by 3 | PDF Full-text (242 KB) | Supplementary Files
Abstract
Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. Structure-based design and synthesis of 1-(4-carboxybutyl)-4-(4-(substituted benzyloxy)phenyl)-1H-pyrrole-2-carboxylic acid derivatives 7a–h, a subset of eight potential FabH inhibitors, is described [...] Read more.
Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. Structure-based design and synthesis of 1-(4-carboxybutyl)-4-(4-(substituted benzyloxy)phenyl)-1H-pyrrole-2-carboxylic acid derivatives 7a–h, a subset of eight potential FabH inhibitors, is described in this paper. The Vilsmeier-Haack reaction was employed as a key step. The structures of all the newly synthesized compounds were identified by IR, 1H-NMR, 13C-NMR, ESI-MS and HRMS. The alamarBlue™ microassay was employed to evaluate the compounds 7a–h against Mycobacterium tuberculosis H37Rv. The results demonstrate that the compound 7d possesses good in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL).These compounds may prove useful in the discovery and development of new anti-tuberculosis drugs. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Preparation of SRN1-Type Coupling Adducts from Aliphatic gem-Dinitro Compounds in Ionic Liquids
Molecules 2012, 17(5), 4782-4790; doi:10.3390/molecules17054782
Received: 29 February 2012 / Revised: 2 April 2012 / Accepted: 12 April 2012 / Published: 25 April 2012
PDF Full-text (212 KB) | Supplementary Files
Abstract
SRN1-type coupling adducts are readily prepared by the reaction between a-sulfonylesters or a-cyanosulfones and gem-dinitro compounds in ionic liquids. The reactions progress smoothly and recovered ionic liquids can be used for several iterations, as long as they are washed [...] Read more.
SRN1-type coupling adducts are readily prepared by the reaction between a-sulfonylesters or a-cyanosulfones and gem-dinitro compounds in ionic liquids. The reactions progress smoothly and recovered ionic liquids can be used for several iterations, as long as they are washed with water to remove alkali metallic salts. The reaction rate is slower than the corresponding SRN1 reaction in DMSO, but no acceleration on irradiation or no inhibition in the presence of m-DNB are observed. Full article
(This article belongs to the Special Issue Ionic Liquids)
Open AccessArticle Comparison of Different Approaches to Define the Applicability Domain of QSAR Models
Molecules 2012, 17(5), 4791-4810; doi:10.3390/molecules17054791
Received: 14 March 2012 / Revised: 13 April 2012 / Accepted: 16 April 2012 / Published: 25 April 2012
Cited by 68 | PDF Full-text (317 KB)
Abstract
One of the OECD principles for model validation requires defining the Applicability Domain (AD) for the QSAR models. This is important since the reliable predictions are generally limited to query chemicals structurally similar to the training compounds used to build the model. [...] Read more.
One of the OECD principles for model validation requires defining the Applicability Domain (AD) for the QSAR models. This is important since the reliable predictions are generally limited to query chemicals structurally similar to the training compounds used to build the model. Therefore, characterization of interpolation space is significant in defining the AD and in this study some existing descriptor-based approaches performing this task are discussed and compared by implementing them on existing validated datasets from the literature. Algorithms adopted by different approaches allow defining the interpolation space in several ways, while defined thresholds contribute significantly to the extrapolations. For each dataset and approach implemented for this study, the comparison analysis was carried out by considering the model statistics and relative position of test set with respect to the training space. Full article
(This article belongs to the Special Issue QSAR and Its Applications)
Open AccessArticle Synthesis of New Indole Derivatives Structurally Related to Donepezil and Their Biological Evaluation as Acetylcholinesterase Inhibitors
Molecules 2012, 17(5), 4811-4823; doi:10.3390/molecules17054811
Received: 26 March 2012 / Revised: 16 April 2012 / Accepted: 17 April 2012 / Published: 25 April 2012
Cited by 7 | PDF Full-text (294 KB) | Supplementary Files
Abstract
New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the [...] Read more.
New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the compounds were found to have potent acetylcholinesterase inhibitor activity compared to donepezil as standard. The compound 1-(2-(4-(2-fluorobenzyl) piperazin-1-yl)acetyl)indoline-2,3-dione (IIId) was found to be the most potent. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Inhibitory Effects of Acetylmelodorinol, Chrysin and Polycarpol from Mitrella kentii on Prostaglandin E2 and Thromboxane B2 Production and Platelet Activating Factor Receptor Binding
Molecules 2012, 17(5), 4824-4835; doi:10.3390/molecules17054824
Received: 26 January 2012 / Revised: 9 April 2012 / Accepted: 10 April 2012 / Published: 26 April 2012
Cited by 5 | PDF Full-text (246 KB)
Abstract
Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E2 (PGE2) and thromboxane B2 (TXB2 [...] Read more.
Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using 3H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE2 production (IC50 value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB2 production with IC50 values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC50 values of 24.3 and 24.5 µM, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antimicrobial and Antioxidant Activities of Essential Oils of Satureja thymbra Growing Wild in Libya
Molecules 2012, 17(5), 4836-4850; doi:10.3390/molecules17054836
Received: 24 February 2012 / Revised: 16 April 2012 / Accepted: 16 April 2012 / Published: 26 April 2012
Cited by 12 | PDF Full-text (222 KB)
Abstract
The composition of essential oil isolated from Satureja thymbra, growing wild in Libya, was analyzed by GC and GC-MS. The essential oil was characterized by γ-terpinene (39.23%), thymol (25.16%), p-cymene (7.17%) and carvacrol (4.18%) as the major constituents. Antioxidant activity was analyzed [...] Read more.
The composition of essential oil isolated from Satureja thymbra, growing wild in Libya, was analyzed by GC and GC-MS. The essential oil was characterized by γ-terpinene (39.23%), thymol (25.16%), p-cymene (7.17%) and carvacrol (4.18%) as the major constituents. Antioxidant activity was analyzed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. It possessed strong antioxidant activity (IC50 = 0.0967 mg/mL). The essential oil was also screened for its antimicrobial activity against eight bacterial and eight fungal species, showing excellent antimicrobial activity against the microorganisms used, in particular against the fungi. The oil of S. thymbra showed bacteriostatic activity at 0.001–0.1 mg/mL and was bactericidal at 0.002–0.2 mg/mL; fungistatic effects at 0.001–0.025 mg/mL and fungicidal effects at 0.001–0.1 mg/mL. The main constituents thymol, carvacrol and γ-terpinene also showed strong antimicrobial activity. The commercial fungicide bifonazole showed much lower antifungal activity than the tested oil. Full article
Open AccessArticle Superconducting Fullerene Nanowhiskers
Molecules 2012, 17(5), 4851-4859; doi:10.3390/molecules17054851
Received: 31 March 2012 / Revised: 12 April 2012 / Accepted: 18 April 2012 / Published: 26 April 2012
Cited by 14 | PDF Full-text (478 KB)
Abstract
We synthesized superconducting fullerene nanowhiskers (C60NWs) by potassium (K) intercalation. They showed large superconducting volume fractions, as high as 80%. The superconducting transition temperature at 17 K was independent of the K content (x) in the range between 1.6 and [...] Read more.
We synthesized superconducting fullerene nanowhiskers (C60NWs) by potassium (K) intercalation. They showed large superconducting volume fractions, as high as 80%. The superconducting transition temperature at 17 K was independent of the K content (x) in the range between 1.6 and 6.0 in K-doped C60 nanowhiskers (KxC60NWs), while the superconducting volume fractions changed with x. The highest shielding fraction of a full shielding volume was observed in the material of K3.3C60NW by heating at 200 °C. On the other hand, that of a K-doped fullerene (K-C60) crystal was less than 1%. We report the superconducting behaviors of our newly synthesized KxC60NWs in comparison to those of KxC60 crystals, which show superconductivity at 19 K in K3C60. The lattice structures are also discussed, based on the x-ray diffraction (XRD) analyses. Full article
(This article belongs to the Special Issue Fullerene Chemistry)
Open AccessArticle The Antimicrobial Efficacy of Elaeis guineensis: Characterization, in Vitro and in Vivo Studies
Molecules 2012, 17(5), 4860-4877; doi:10.3390/molecules17054860
Received: 6 March 2012 / Revised: 14 April 2012 / Accepted: 16 April 2012 / Published: 26 April 2012
Cited by 9 | PDF Full-text (1564 KB)
Abstract
The urgent need to treat multi-drug resistant pathogenic microorganisms in chronically infected patients has given rise to the development of new antimicrobials from natural resources. We have tested Elaeis guineensis Jacq (Arecaceae) methanol extract against a variety of bacterial, fungal and yeast [...] Read more.
The urgent need to treat multi-drug resistant pathogenic microorganisms in chronically infected patients has given rise to the development of new antimicrobials from natural resources. We have tested Elaeis guineensis Jacq (Arecaceae) methanol extract against a variety of bacterial, fungal and yeast strains associated with infections. Our studies have demonstrated that E. guineensis exhibits excellent antimicrobial activity in vitro and in vivo against the bacterial and fungal strains tested. A marked inhibitory effect of the E. guineensis extracts was observed against C. albicans whereby E. guineensis extract at ½, 1, or 2 times the MIC significantly inhibited C. albicans growth with a noticeable drop in optical density (OD) of the bacterial culture. This finding confirmed the anticandidal activity of the extract on C. albicans. Imaging using scanning (SEM) and transmission (TEM) electron microscopy was done to determine the major alterations in the microstructure of the extract-treated C. albicans. The main abnormalities noted via SEM and TEM studies were the alteration in morphology of the yeast cells. In vivo antimicrobial activity was studies in mice that had been inoculated with C. albicans and exhibited good anticandidal activity. The authors conclude that the extract may be used as a candidate for the development of anticandidal agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Kinetic Study of Oxygen Adsorption over Nanosized Au/γ-Al2O3 Supported Catalysts under Selective CO Oxidation Conditions
Molecules 2012, 17(5), 4878-4895; doi:10.3390/molecules17054878
Received: 13 February 2012 / Revised: 8 April 2012 / Accepted: 18 April 2012 / Published: 27 April 2012
Cited by 5 | PDF Full-text (402 KB)
Abstract
O2 adsorption is a key process for further understanding the mechanism of selective CO oxidation (SCO) on gold catalysts. Rate constants related to the elementary steps of O2 adsorption, desorption and surface bonding, as well as the respective activation energies, [...] Read more.
O2 adsorption is a key process for further understanding the mechanism of selective CO oxidation (SCO) on gold catalysts. Rate constants related to the elementary steps of O2 adsorption, desorption and surface bonding, as well as the respective activation energies, over a nanosized Au/γ-Al2O3 catalyst, were determined by Reversed-Flow Inverse Gas Chromatography (RF-IGC). The present study, carried-out in a wide temperature range (50–300 °C), both in excess as well as in the absence of H2, resulted in mechanistic insights and kinetic as well as energetic comparisons, on the sorption processes of SCO reactants. In the absence of H2, the rate of O2 binding, over Au/γ-Al2O3, drastically changes with rising temperature, indicating possible O2 dissociation at elevated temperatures. H2 facilitates stronger O2 bonding at higher temperatures, while low temperature binding remains practically unaffected. The lower energy barriers observed, under H2 rich conditions, can be correlated to O2 dissociation after hydrogenation. Although, H2 enhances both selective CO reactant’s desorption, O2 desorption is more favored than that of CO, in agreement with the well-known mild bonding of SCO reactant’s at lower temperatures. The experimentally observed drastic change in the strength of CO and O2 binding is consistent both with well-known high activity of SCO at ambient temperatures, as well as with the loss of selectivity at higher temperatures. Full article
(This article belongs to the Special Issue Gold Catalysts)
Open AccessArticle Gossypol Exhibits a Strong Influence Towards UDP-Glucuronosyltransferase (UGT) 1A1, 1A9 and 2B7-Mediated Metabolism of Xenobiotics and Endogenous Substances
Molecules 2012, 17(5), 4896-4903; doi:10.3390/molecules17054896
Received: 19 March 2012 / Revised: 8 April 2012 / Accepted: 16 April 2012 / Published: 27 April 2012
Cited by 15 | PDF Full-text (224 KB)
Abstract
Gossypol, the polyphenolic constituent isolated from cottonseeds, has been used as a male antifertility drug for a long time, and has been demonstrated to exhibit excellent anti-tumor activity towards multiple cancer types. The toxic effects of gossypol limit its clinical utilization, and [...] Read more.
Gossypol, the polyphenolic constituent isolated from cottonseeds, has been used as a male antifertility drug for a long time, and has been demonstrated to exhibit excellent anti-tumor activity towards multiple cancer types. The toxic effects of gossypol limit its clinical utilization, and enzyme inhibition is an important facet of this. In the present study, in vitro human liver microsomal incubation system supplemented with UDPGA was used to investigate the inhibition of gossypol towards UGT1A1, 1A9 and 2B7-mediated metabolism of xenobiotics and endogenous substances. Estradiol, the probe substrate of UGT1A1, was selected as representative endogenous substance. Propofol (a probe substrate of UGT1A9) and 3'-azido-3'-deoxythimidine (AZT, a probe substrate of UGT2B7) were employed as representative xenobiotics. The results showed that gossypol noncompetitively inhibits UGT-mediated estradiol-3-glucuronidation and propofol O-glucuronidation, and the inhibition kinetic parameters (Ki) were calculated to be 34.2 and 16.4 μM, respectively. Gossypol was demonstrated to exhibit competitive inhibition towards UGT-mediated AZT glucuronidation, and the inhibition kinetic parameter (Ki) was determined to be 14.0 μM. All these results indicated that gossypol might induce metabolic disorders of endogenous substances and alteration of metabolic behaviour of co-administered xenobiotics through inhibition of UGTs’ activity. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Microbial Enhance of Chitosan Production by Rhizopus arrhizus Using Agroindustrial Substrates
Molecules 2012, 17(5), 4904-4914; doi:10.3390/molecules17054904
Received: 9 February 2012 / Revised: 16 April 2012 / Accepted: 26 April 2012 / Published: 27 April 2012
Cited by 12 | PDF Full-text (530 KB)
Abstract
This study investigated the potential of Rhizopus arrhizus UCP 402 for producing chitosan using corn steep liquor and honey as agroindustrial nitrogen and carbon sources. A complete factorial design was used to assess the improved biomass and chitosan production. The results were [...] Read more.
This study investigated the potential of Rhizopus arrhizus UCP 402 for producing chitosan using corn steep liquor and honey as agroindustrial nitrogen and carbon sources. A complete factorial design was used to assess the improved biomass and chitosan production. The results were evaluated using Pareto charts (Statistica 7.0 software). The chitosan obtained was characterized by X-ray diffraction. The cristallinity index (IC), and infrared spectroscopy (FTIR) were used to evaluate the degree of deacetylation (DD %). The morphological aspects of the R. arrhizus were evaluated by measuring the diameter of the colonies by light microscopy. The results obtained showed higher biomass and chitosan yields (20.61 g/L and 29.3 mg/g), respectively, in the selected assays. The characterization of the macromolecular arrangement of chitosan showed a crystallinity index compatible with the literature, and the infrared peaks confirmed a degree of 86%. The experimental data obtained suggest that adding honey to corn steep liquor is a promising way to improve microbiological chitosan production. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Suffruyabiosides A and B, Two New Monoterpene Diglycosides from Moutan Cortex
Molecules 2012, 17(5), 4915-4923; doi:10.3390/molecules17054915
Received: 14 April 2012 / Revised: 16 April 2012 / Accepted: 16 April 2012 / Published: 30 April 2012
Cited by 8 | PDF Full-text (251 KB)
Abstract
Two new monoterpene diglycosides, suffruyabiosides A (1) and B (2), and seven known compounds 39 were isolated from Moutan Cortex (root cortex of Paeonia suffruticosa Andrews). The structures were elucidated on the basis of 2D NMR [...] Read more.
Two new monoterpene diglycosides, suffruyabiosides A (1) and B (2), and seven known compounds 39 were isolated from Moutan Cortex (root cortex of Paeonia suffruticosa Andrews). The structures were elucidated on the basis of 2D NMR spectral data. Suffruyabiosides A (1) and B (2) are rare monoterpene diglycosides, including a cellobiose in the molecules. Salicylpaeoniflorin (4) had a antiproliferation effect similar to paeoniflorin (3) on human lung adenocarcinoma epitherial A549 cells. Galloylpaeoniflorin (8) and salicylpaeoniflorin (4) revealed a more pronounced radical scavenging effect than a-tocopherol (positive control). An increase in the number of phenolic hydroxyl groups produced a more effective radical scavenging effect [8 > mudanpioside E (6) > oxypaeoniflorin (5)]. Comparison of the effects of 4 and 5 showed that o-substitution with a phenolic hydroxyl group was more effective than p-substitution. The results suggest that salicylpaeoniflorin (4) may be useful as a cytotoxic and a radical scavenging agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A New and Efficient Method for the Synthesis of 3,4-Disubstituted Pyrrolidine-2,5-diones
Molecules 2012, 17(5), 4936-4949; doi:10.3390/molecules17054936
Received: 12 March 2012 / Revised: 18 April 2012 / Accepted: 20 April 2012 / Published: 30 April 2012
Cited by 5 | PDF Full-text (259 KB)
Abstract A newly found reaction for the synthesis of 3,4-disubstituted 1-hydroxy-pyrrolidine-2,5-diones from 3-substituted coumarins and nitromethane has been elaborated. The reaction involved a simple and convenient experimental procedure. The applicability of the rearrangement reaction is determined. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle MALDI-TOF MS Analysis of Native and Permethylated or Benzimidazole-Derivatized Polysaccharides
Molecules 2012, 17(5), 4950-4961; doi:10.3390/molecules17054950
Received: 20 December 2011 / Revised: 6 April 2012 / Accepted: 20 April 2012 / Published: 30 April 2012
Cited by 10 | PDF Full-text (336 KB)
Abstract
MALDI-TOF MS provides rapid and sensitive analyses of larger biomolecules. However, MS analyses of polysaccharide have been reported to have lower sensitivity compared to peptides and proteins. Here, we investigated some polysaccharides chemically derivatized by permethylation and ortho-phenylene diamine (OPD) tagging. [...] Read more.
MALDI-TOF MS provides rapid and sensitive analyses of larger biomolecules. However, MS analyses of polysaccharide have been reported to have lower sensitivity compared to peptides and proteins. Here, we investigated some polysaccharides chemically derivatized by permethylation and ortho-phenylene diamine (OPD) tagging. Methylated glycan is obviously able to improve the sensitivity for mass spectrometry detection. Oxidative condensation by UV-activation tagging to saccharides by OPD and peptide-OPD also improve the sensitivity of MALDI-TOF MS analyses. Polysaccharides including dextran, glucomannan, arabinoxylan, arabinogalactan and beta-1,3-glucan, isolated from nutritional supplements of Ganoderma lucidum and Saccharomyces pastorianus were measured using MALDI-TOF MS with 2,5-dihydroxybenzoic acid (2,5-DHB) as the matrix. These glycans were also derivatized to methylated and benzimidazole-tagged glycans by chemical transformation for molecular weight analysis. The derivatized polysaccharides showed excellent MALDI-TOF MS signal enhancement in the molecular weight range from 1 to 5 kDa. Here, we demonstrate an efficient method to give glycan-benzimidazole (glycan-BIM) derivatives for polysaccharide determination in MALDI-TOF MS. Therefore, permethylated or benzimidazole-derivatized polysaccharides provide a new option for polysaccharide analysis using MALDI-TOF MS. Full article
(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)
Open AccessArticle Synthesis and Antimicrobial Evaluation of Some Pyrazole Derivatives
Molecules 2012, 17(5), 4962-4971; doi:10.3390/molecules17054962
Received: 20 February 2012 / Revised: 23 March 2012 / Accepted: 18 April 2012 / Published: 30 April 2012
Cited by 14 | PDF Full-text (325 KB)
Abstract
Reaction of a series of (E)-3-phenyl-4-(p-substituted phenyl)-3-buten-2-ones with p-sulfamylphenyl hydrazine in glacial acetic acid gave the corresponding hydrazones, subsequent treatment of which with 30% HCl afforded pyrazole-1-sulphonamides. On the other hand, refluxing of chalcones with either thiosemicarbazide or [...] Read more.
Reaction of a series of (E)-3-phenyl-4-(p-substituted phenyl)-3-buten-2-ones with p-sulfamylphenyl hydrazine in glacial acetic acid gave the corresponding hydrazones, subsequent treatment of which with 30% HCl afforded pyrazole-1-sulphonamides. On the other hand, refluxing of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide in ethanol containing a few drops of acetic acid gave pyrazoline-1-thiocarboxamides and isonicotinoyl pyrazolines, respectively. The structures of the synthesized compounds were determined on the basis of their elemental analyses and spectroscopic data. The antimicrobial activity of the newly isolated heterocyclic compounds was evaluated against Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed a moderate degree of potent antimicrobial activity. Full article
(This article belongs to the Special Issue Heterocycles)
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Open AccessArticle Synthesis and Biological Evaluation of New Ligustrazine Derivatives as Anti-Tumor Agents
Molecules 2012, 17(5), 4972-4985; doi:10.3390/molecules17054972
Received: 19 March 2012 / Revised: 18 April 2012 / Accepted: 20 April 2012 / Published: 30 April 2012
Cited by 25 | PDF Full-text (403 KB) | Supplementary Files
Abstract
To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the “combination principle” in drug discovery. The ligustrazine derivatives’ [...] Read more.
To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the “combination principle” in drug discovery. The ligustrazine derivatives’ anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (4) and 3 α,12 α-dihydroxy-5β-dholanic acid-3,5,6-trimethylpyrazin-2-methyl ester (5) not only displayed antiproliferative activities on these cancer cells, but also dramatically suppressed normal angiogenesis in CAM. The LD50 value of the compound 5 exceeded 3.0 g/kg by oral administration in mice. Full article
Open AccessArticle Bioassay-Guided Antidiabetic Study of Phaleria macrocarpa Fruit Extract
Molecules 2012, 17(5), 4986-5002; doi:10.3390/molecules17054986
Received: 11 January 2012 / Revised: 5 April 2012 / Accepted: 12 April 2012 / Published: 30 April 2012
Cited by 11 | PDF Full-text (1266 KB)
Abstract
An earlier anti-hyperglycemic study with serial crude extracts of Phaleria macrocarpa (PM) fruit indicated methanol extract (ME) as the most effective. In the present investigation, the methanol extract was further fractionated to obtain chloroform (CF), ethyl acetate (EAF), n-butanol (NBF) and aqueous (AF) fractions, which were tested for antidiabetic activity. The NBF reduced blood glucose (p < 0.05) 15 min after administration, in an intraperitoneal glucose tolerance test (IPGTT) similar to metformin. Moreover, it lowered blood glucose in diabetic rats by 66.67% (p < 0.05), similar to metformin (51.11%), glibenclamide (66.67%) and insulin (71.43%) after a 12-day treatment, hence considered to be the most active fraction. Further fractionation of NBF yielded sub-fractions I (SFI) and II (SFII), and only SFI lowered blood glucose (p < 0.05), in IPGTT similar to glibenclamide. The ME, NBF, and SFI correspondingly lowered plasma insulin (p < 0.05) and dose-dependently inhibited glucose transport across isolated rat jejunum implying an extra-pancreatic mechanism. Phytochemical screening showed the presence of flavonoids, terpenes and tannins, in ME, NBF and SFI, and LC-MS analyses revealed 9.52%, 33.30% and 22.50% mangiferin respectively. PM fruit possesses anti-hyperglycemic effect, exerted probably through extra-pancreatic action. Magniferin, contained therein may be responsible for this reported activity. Full article
Open AccessArticle Glycosylation of Vanillin and 8-Nordihydrocapsaicin by Cultured Eucalyptus perriniana Cells
Molecules 2012, 17(5), 5013-5020; doi:10.3390/molecules17055013
Received: 29 March 2012 / Revised: 17 April 2012 / Accepted: 23 April 2012 / Published: 2 May 2012
Cited by 4 | PDF Full-text (219 KB) | Supplementary Files
Abstract
Glycosylation of vanilloids such as vanillin and 8-nordihydrocapsaicin by cultured plant cells of Eucalyptus perriniana was studied. Vanillin was converted into vanillin 4-O-b-D-glucopyranoside, vanillyl alcohol, and 4-O-b-D-glucopyranosylvanillyl alcohol by E. perriniana cells. Incubation of cultured E. perriniana cells [...] Read more.
Glycosylation of vanilloids such as vanillin and 8-nordihydrocapsaicin by cultured plant cells of Eucalyptus perriniana was studied. Vanillin was converted into vanillin 4-O-b-D-glucopyranoside, vanillyl alcohol, and 4-O-b-D-glucopyranosylvanillyl alcohol by E. perriniana cells. Incubation of cultured E. perriniana cells with 8-nor- dihydrocapsaicin gave 8-nordihydrocapsaicin 4-O-b-D-glucopyranoside and 8-nordihydro- capsaicin 4-O-b-D-gentiobioside. Full article
(This article belongs to the Special Issue Advances in Carbohydrate Chemistry 2012)
Open AccessArticle Synthesis and Characterization of ZnO Nanowires by Thermal Oxidation of Zn Thin Films at Various Temperatures
Molecules 2012, 17(5), 5021-5029; doi:10.3390/molecules17055021
Received: 29 February 2012 / Revised: 16 April 2012 / Accepted: 28 April 2012 / Published: 2 May 2012
Cited by 18 | PDF Full-text (884 KB)
Abstract
In this research high-quality zinc oxide (ZnO) nanowires have been synthesized by thermal oxidation of metallic Zn thin films. Metallic Zn films with thicknesses of 250 nm have been deposited on a glass substrate by the PVD technique. The deposited zinc thin [...] Read more.
In this research high-quality zinc oxide (ZnO) nanowires have been synthesized by thermal oxidation of metallic Zn thin films. Metallic Zn films with thicknesses of 250 nm have been deposited on a glass substrate by the PVD technique. The deposited zinc thin films were oxidized in air at various temperatures ranging between 450 °C to 650 °C. Surface morphology, structural and optical properties of the ZnO nanowires were examined by scanning electron microscope (SEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX) and photoluminescence (PL) measurements. XRD analysis demonstrated that the ZnO nanowires has a wurtzite structure with orientation of (002), and the nanowires prepared at 600 °C has a better crystalline quality than samples prepared at other temperatures. SEM results indicate that by increasing the oxidation temperature, the dimensions of the ZnO nanowires increase. The optimum temperature for synthesizing high density, ZnO nanowires was determined to be 600 °C. EDX results revealed that only Zn and O are present in the samples, indicating a pure ZnO composition. The PL spectra of as-synthesized nanowires exhibited a strong UV emission and a relatively weak green emission. Full article
Open AccessArticle Chemical Composition, Antimicrobial and Antitumor Activities of the Essential Oils and Crude Extracts of Euphorbia macrorrhiza
Molecules 2012, 17(5), 5030-5039; doi:10.3390/molecules17055030
Received: 21 March 2012 / Revised: 17 April 2012 / Accepted: 20 April 2012 / Published: 3 May 2012
Cited by 15 | PDF Full-text (254 KB)
Abstract
The present study aimed to examine the chemical composition and biological activity of essential oils extracted from Euphorbia macrorrhiza collected from Northwest China. The major constituents of the essential oils of aerial parts and roots of E. macrorrhiza are acorenone B (16.72% [...] Read more.
The present study aimed to examine the chemical composition and biological activity of essential oils extracted from Euphorbia macrorrhiza collected from Northwest China. The major constituents of the essential oils of aerial parts and roots of E. macrorrhiza are acorenone B (16.72% and 25.80%), (+)-cycloisosativene (14.94% and 12.40%), 3a-hydroxy-5b-androstane (10.62% and 5.52%), copaene (7.37% and 6.29%), l-calamenene (4.13% and 4.65%) and β-cedrene (8.40% and 7.98%), respectively. The minor components of them are thymene, γ-terpinene, thymecamphor, α-cedrene, zingiberene, trans-caryophyllene, β-chamigrene, curcumene, pentadecane, (−)-α-muurolene, cuparene, γ-cadinene, (Z)-3-heptadecene, 1,3,7,7-tetramethyl-2-oxabicyclo(4.4.0)dec-5-en-4-one, hexahydrofarnesyl acetone, γ-elixene and palmitinic acid. The antimicrobial and antitumor activitiy of the E. macrorrhiza essential oil against Staphyloccocus aureus, Escherichia coli, Canidia Albicans and Caco-2 cells were evaluated. Among all the tested microorganisms and Caco-2 cells, the essential oils showed the strongest inhibitory effect on Staphyloccocus aureus (MIC = 2.8 μg/mL) and Caco-2 cell (IC50 = 11.86 μg/mL), whereas no effect on Escherichia coli and Candida albicans. The data of this study suggested that the E. macrorrhiza essential oils have great potential as a natural medicine for microbial infections and cancers. Full article
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Open AccessCommunication Synthesis and Characterization of 5-Nitro-2-nitratomethyl-1,2,3,4-tetrazole: A High Nitrogen Energetic Compound with Good Oxygen Balance
Molecules 2012, 17(5), 5040-5049; doi:10.3390/molecules17055040
Received: 29 February 2012 / Revised: 18 April 2012 / Accepted: 20 April 2012 / Published: 3 May 2012
Cited by 15 | PDF Full-text (327 KB)
Abstract
The synthesis of 5-nitro-2-nitratomethyl-1,2,3,4-tetrazole (4) and its full characterization are given here. Compound 4 was synthesized through the nitration of 5-nitro-2-hydroxymethyl-tetrazole (3) with fuming nitric acid and acetic anhydride and its structure was characterized by MS, FT-IR, 1 [...] Read more.
The synthesis of 5-nitro-2-nitratomethyl-1,2,3,4-tetrazole (4) and its full characterization are given here. Compound 4 was synthesized through the nitration of 5-nitro-2-hydroxymethyl-tetrazole (3) with fuming nitric acid and acetic anhydride and its structure was characterized by MS, FT-IR, 1H-NMR and 13C-NMR techniques. The crystal structure of 4 was determined by X-ray single crystal diffraction analysis. The compound belongs to the orthorhombic system with space group Pna2(1), and its crystal parameters were a = 2.121(8) nm, b = 0.5281(19) nm, c = 0.6246(2) nm, Z = 4, V = 0.6995(4) nm3, Dc = 1.805 g/cm3, F(000) = 384, μ = 0.174 mm−1. A theoretical study of 4 has been performed, using quantum computational density functional theory (B3LYP methods) with 6-31G* basis sets as implemented in the Gaussian 03 program suite. The obtained heat of formation (HOF) for 4 was 228.07 kJ·mol−1, the detonation pressure (P) values calculated for 4 was 37.92 GPa, the detonation velocity (D) can reach 9260 m·s−1, and the oxygen balance was zero (Q), making 4 a competitive energetic compound. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Assessment of Genetic Fidelity in Rauvolfia serpentina Plantlets Grown from Synthetic (Encapsulated) Seeds Following in Vitro Storage at 4 °C
Molecules 2012, 17(5), 5050-5061; doi:10.3390/molecules17055050
Received: 27 March 2012 / Revised: 17 April 2012 / Accepted: 20 April 2012 / Published: 3 May 2012
Cited by 20 | PDF Full-text (431 KB)
Abstract
An efficient method was developed for plant regeneration and establishment from alginate encapsulated synthetic seeds of Rauvolfia serpentina. Synthetic seeds were produced using in vitro proliferated microshoots upon complexation of 3% sodium alginate prepared in Llyod and McCown woody plant medium [...] Read more.
An efficient method was developed for plant regeneration and establishment from alginate encapsulated synthetic seeds of Rauvolfia serpentina. Synthetic seeds were produced using in vitro proliferated microshoots upon complexation of 3% sodium alginate prepared in Llyod and McCown woody plant medium (WPM) and 100 mM calcium chloride. Re-growth ability of encapsulated nodal segments was evaluated after storage at 4 °C for 0, 1, 2, 4, 6 and 8 weeks and compared with non-encapsulated buds. Effects of different media viz; Murashige and Skoog medium; Lloyd and McCown woody Plant medium, Gamborg’s B5 medium and Schenk and Hildebrandt medium was also investigated for conversion into plantlets. The maximum frequency of conversion into plantlets from encapsulated nodal segments stored at 4 °C for 4 weeks was achieved on woody plant medium supplement with 5.0 μM BA and 1.0 μM NAA. Rooting in plantlets was achieved in half-strength Murashige and Skoog liquid medium containing 0.5 μM indole-3-acetic acid (IAA) on filter paper bridges. Plantlets obtained from stored synseeds were hardened, established successfully ex vitro and were morphologically similar to each other as well as their mother plant. The genetic fidelity of Rauvolfia clones raised from synthetic seeds following four weeks of storage at 4 °C were assessed by using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers. All the RAPD and ISSR profiles from generated plantlets were monomorphic and comparable to the mother plant, which confirms the genetic stability among the clones. This synseed protocol could be useful for establishing a particular system for conservation, short-term storage and production of genetically identical and stable plants before it is released for commercial purposes. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle Tentative Identification of Volatile Flavor Compounds in Commercial Budu, a Malaysian Fish Sauce, Using GC-MS
Molecules 2012, 17(5), 5062-5080; doi:10.3390/molecules17055062
Received: 19 December 2011 / Revised: 12 April 2012 / Accepted: 13 April 2012 / Published: 3 May 2012
Cited by 10 | PDF Full-text (362 KB)
Abstract
Budu is a famous Malaysian fish sauce, usually used as seasoning and condiment in cooking. Budu is produced by mixing fish and salt at certain ratio followed by fermentation for six months in closed tanks. In this study, four commercial brands of [...] Read more.
Budu is a famous Malaysian fish sauce, usually used as seasoning and condiment in cooking. Budu is produced by mixing fish and salt at certain ratio followed by fermentation for six months in closed tanks. In this study, four commercial brands of Budu were analyzed for their chemical properties (pH, salt content and volatile compounds). The pH of Budu samples ranged from 4.50–4.92, while the salt (NaCl) content ranged between 11.80% and 22.50% (w/v). For tentative identification of volatile flavor compounds in Budu, two GC columns have been used, DB-WAX and HP-5MS. A total of 44 volatile compounds have been detected and 16 were common for both columns. 3-Methyl-1-butanol, 2-methylbutanal, 3-methylbutanal, dimethyl disulfide, 3-(methylthio)-propanal, 3-methylbutanoic acid and benzaldehye have been identified as the aroma-active compounds in Budu due to their lower threshold values. Full article
Open AccessArticle A Convenient One-Pot Preparation of 2-Methyl-3-(phenylthio- methyl)quinolines from Morita-Baylis-Hillman Adducts and Their Oxidation to the Corresponding Sulfones
Molecules 2012, 17(5), 5081-5094; doi:10.3390/molecules17055081
Received: 7 March 2012 / Revised: 19 April 2012 / Accepted: 20 April 2012 / Published: 3 May 2012
Cited by 3 | PDF Full-text (245 KB) | Supplementary Files
Abstract A convenient one-pot preparation of 2-methyl-3-(phenylthiomethyl)quinolines from Morita-Baylis-Hillman adducts via conjugate addition of thiols followed by reductive cyclization with Fe/AcOH was developed. The 2-methyl-3-(phenylthiomethyl)quinolines were transformed into 2-methyl-3-(phenylsulfonylmethyl)quinolines via m-CPBA-mediated oxidation. Full article
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Open AccessArticle Synthesis, Molecular Properties Prediction, and Anti-staphylococcal Activity of N-Acylhydrazones and New 1,3,4-Oxadiazole Derivatives
Molecules 2012, 17(5), 5095-5107; doi:10.3390/molecules17055095
Received: 19 March 2012 / Revised: 18 April 2012 / Accepted: 19 April 2012 / Published: 3 May 2012
Cited by 13 | PDF Full-text (194 KB)
Abstract
Five new 1-(2-(5-nitrofuran-2-yl)-5-(aryl)-1,3,4-oxadiazol-3-(2H)-yl) ethanone compounds 5a–e were synthesized by cyclization of N-acylhydrazones 4a–e with acetic anhydride under reflux conditions. Their structures were fully characterized by IR, 1H-NMR, and 13C-NMR. Furthermore, evaluations of the antibacterial activity of the [...] Read more.
Five new 1-(2-(5-nitrofuran-2-yl)-5-(aryl)-1,3,4-oxadiazol-3-(2H)-yl) ethanone compounds 5a–e were synthesized by cyclization of N-acylhydrazones 4a–e with acetic anhydride under reflux conditions. Their structures were fully characterized by IR, 1H-NMR, and 13C-NMR. Furthermore, evaluations of the antibacterial activity of the 1,3,4-oxadiazoles 5a–e and N-acylhydrazones 4a–e showed strong activity against several strains of Staphylococcus aureus, with MICs between 4 μg/mL to 32 μg/mL. In silico studies of the parameters of Lipinski’s Rule of Five, as well as the topological polar surface area (TPSA), absorption percentage (% ABS), drug likeness and drug score indicate that these compounds, especially 4a and 5d, have potential to be new drug candidates. Full article
Open AccessArticle Absorption and Fluorescence Spectroscopic Properties of 1- and 1,4-Silyl-Substituted Naphthalene Derivatives
Molecules 2012, 17(5), 5108-5125; doi:10.3390/molecules17055108
Received: 13 February 2012 / Revised: 21 April 2012 / Accepted: 23 April 2012 / Published: 3 May 2012
Cited by 24 | PDF Full-text (688 KB)
Abstract
Silyl-substituted naphthalene derivatives at the 1- and 1,4-positions were synthesized and their UV absorption, fluorescence spectroscopic properties, and fluorescence lifetimes were determined. Analysis of the results shows that the introduction of silyl groups at these positions of the naphthalene chromophore/fluorophore causes shifts [...] Read more.
Silyl-substituted naphthalene derivatives at the 1- and 1,4-positions were synthesized and their UV absorption, fluorescence spectroscopic properties, and fluorescence lifetimes were determined. Analysis of the results shows that the introduction of silyl groups at these positions of the naphthalene chromophore/fluorophore causes shifts of the absorption maxima to longer wavelengths and increases in fluorescence intensities. Bathochromic shifts of the absorption maxima and increases in fluorescence intensities are also promoted by the introduction of methoxy and cyano groups at the naphthalene 4- and 5-positions. In addition, the fluorescence of 9,10-dicyanoanthracene is efficiently quenched by these naphthalene derivatives with Stern-Volmer plot calculated rate constants that depend on the steric bulk of the silyl groups. Full article
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Open AccessArticle Comparison of the Simple Cyclic Voltammetry (CV) and DPPH Assays for the Determination of Antioxidant Capacity of Active Principles
Molecules 2012, 17(5), 5126-5138; doi:10.3390/molecules17055126
Received: 2 March 2012 / Revised: 12 April 2012 / Accepted: 25 April 2012 / Published: 3 May 2012
Cited by 33 | PDF Full-text (777 KB)
Abstract
Antioxidant activity of a number of small (low molecular weight) natural compounds found in spices, condiments or drugs (gallic acid, sesamol, eugenol, thymol, carvacrol, vanillin, salicylaldehyde, limonene, geraniol, 4-hexylresorcinol, etc.) has been evaluated using electrochemical and DPPH radical scavenging measurements. [...] Read more.
Antioxidant activity of a number of small (low molecular weight) natural compounds found in spices, condiments or drugs (gallic acid, sesamol, eugenol, thymol, carvacrol, vanillin, salicylaldehyde, limonene, geraniol, 4-hexylresorcinol, etc.) has been evaluated using electrochemical and DPPH radical scavenging measurements. Structural analysis of the tested compound suggest a remarkable activity for phenol derivatives and the importance of the –R groups located on the phenolic ring in the molecule’s ability to act as free radical scavenging as well as their influence in the electrochemical behavior. The voltammetric method can be used for the determination of the antioxidant capability in the same manner as the DPPH radical scavenging because of the correlation found between oxidation potentials and anti-radical power (ARP = 1/EC50). Such electrochemical determination is fast and cheap and allows making measurements under a variety of experimental conditions. The accuracy of the electrochemical measurements is the same for all the compounds, irrespective of their scavenging activity, the opposite of what occurs in the DPPH test. Full article
Open AccessArticle Synthesis and Bioactivity of Pyrazole Acyl Thiourea Derivatives
Molecules 2012, 17(5), 5139-5150; doi:10.3390/molecules17055139
Received: 11 April 2012 / Revised: 19 April 2012 / Accepted: 19 April 2012 / Published: 3 May 2012
Cited by 14 | PDF Full-text (269 KB)
Abstract
Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate [...] Read more.
Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, 1H-NMR, 13C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests. Full article
Open AccessCommunication A Facile One-Pot Process for the Formation of Hindered Tertiary Amines
Molecules 2012, 17(5), 5151-5163; doi:10.3390/molecules17055151
Received: 4 April 2012 / Revised: 25 April 2012 / Accepted: 25 April 2012 / Published: 3 May 2012
Cited by 3 | PDF Full-text (232 KB) | Supplementary Files
Abstract
A simple and convenient method was developed for the preparation of hindered tertiary amines via direct reductive amination of ketones with secondary aryl amines, using trichlorosilane as reducing agent and tetramethylethylenediamine (TMEDA) as organic Lewis base activator. A broad range of ketones [...] Read more.
A simple and convenient method was developed for the preparation of hindered tertiary amines via direct reductive amination of ketones with secondary aryl amines, using trichlorosilane as reducing agent and tetramethylethylenediamine (TMEDA) as organic Lewis base activator. A broad range of ketones were reacted with N-methylaniline to afford the corresponding tertiary amine products in high yield. An open transition model was proposed for the reductive step. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Microwave-assisted Solvent-free Synthesis and in Vitro Antibacterial Screening of Quinoxalines and Pyrido[2, 3b]pyrazines
Molecules 2012, 17(5), 5164-5176; doi:10.3390/molecules17055164
Received: 15 March 2012 / Revised: 22 April 2012 / Accepted: 23 April 2012 / Published: 4 May 2012
Cited by 8 | PDF Full-text (241 KB)
Abstract
We report herein the microwave assisted synthesis, without solvents and catalysts, of 6-substituted quinoxalines and 7-substituted pyrido[2,3b]pyrazines. The compounds were obtained in good yields and short reaction times using the mentioned procedure and two new structures are reported. A complete [...] Read more.
We report herein the microwave assisted synthesis, without solvents and catalysts, of 6-substituted quinoxalines and 7-substituted pyrido[2,3b]pyrazines. The compounds were obtained in good yields and short reaction times using the mentioned procedure and two new structures are reported. A complete 1H- and 13C-NMR assignment was performed using 1D and 2D-NMR. Additionally, an in vitro screening was performed on Gram-positive and Gram-negative bacteria using amoxicillin as positive reference. Compounds bearing a pyridyl group tended to have higher antibacterial activity, but the best activity against Bacillus subtilis and Proteus mirabilis was observed with quinoxaline derivatives. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessCommunication Synthesis of Electronically Modified Ru-Based Neutral 16 VE Allenylidene Olefin Metathesis Precatalysts
Molecules 2012, 17(5), 5177-5186; doi:10.3390/molecules17055177
Received: 1 April 2012 / Revised: 25 April 2012 / Accepted: 26 April 2012 / Published: 4 May 2012
Cited by 7 | PDF Full-text (359 KB)
Abstract
Electronic modifications within Ru-based olefin metathesis precatalysts have provided a number of new complexes with significant differences in reactivity profiles. So far, this aspect has not been studied for neutral 16 VE allenylidenes. The first synthesis of electronically altered complexes of this [...] Read more.
Electronic modifications within Ru-based olefin metathesis precatalysts have provided a number of new complexes with significant differences in reactivity profiles. So far, this aspect has not been studied for neutral 16 VE allenylidenes. The first synthesis of electronically altered complexes of this type is reported. Following the classical dehydration approach (vide infra) modified propargyl alcohols were transformed to the targeted allenylidene systems in the presence of PCy3. The catalytic performance was investigated in RCM reaction (ring closing metathesis) of benchmark substrates such as diallyltosylamide (6) and diethyl diallylmalonate (7). Full article
(This article belongs to the Special Issue Olefin Metathesis and Its Application)
Open AccessArticle Diterpenoid Alkaloids from the Chinese Traditional Herbal “Fuzi” and Their Cytotoxic Activity
Molecules 2012, 17(5), 5187-5194; doi:10.3390/molecules17055187
Received: 21 March 2012 / Revised: 23 April 2012 / Accepted: 24 April 2012 / Published: 4 May 2012
Cited by 15 | PDF Full-text (212 KB)
Abstract
Ten diterpenoid alkaloids, including eight aconitine-type C19-diterpenoid alkaloids and two hetisine-type C20-diterpenoid alkaloids, were isolated from the secondary roots of Aconitum carmichaeli Debx., known as “Fuzi” in Chinese traditional herbal medicine. Their structures were established on the basis [...] Read more.
Ten diterpenoid alkaloids, including eight aconitine-type C19-diterpenoid alkaloids and two hetisine-type C20-diterpenoid alkaloids, were isolated from the secondary roots of Aconitum carmichaeli Debx., known as “Fuzi” in Chinese traditional herbal medicine. Their structures were established on the basis of their spectroscopic data and comparison with those of the literature. Among these alkaloids, chasmanine, oxonitine and 15-acetylsongoramine were isolated for the first time from this medicinal plant. The cytotoxic activity of the alkaloids were tested against several cell lines by the MTT method in which aconitine, hypaconitine, mesaconitne and oxonitine were found to strongly inhibit the growth of the HePG2 cell line, which showed that the existence and quantity of the ester groups have a significant influence on the cytotoxicity of the diterpenoid alkaloids. Full article
Open AccessArticle Impact of Elevated Carbon Dioxide on Primary, Secondary Metabolites and Antioxidant Responses of Eleais guineensis Jacq. (Oil Palm) Seedlings
Molecules 2012, 17(5), 5195-5211; doi:10.3390/molecules17055195
Received: 27 February 2012 / Revised: 21 April 2012 / Accepted: 23 April 2012 / Published: 4 May 2012
Cited by 13 | PDF Full-text (246 KB)
Abstract
A split plot 3 by 3 experiment was designed to investigate the relationships among production of primary metabolites (soluble sugar and starch), secondary metabolites (total flavonoids, TF; total phenolics, TP), phenylalanine lyase (PAL) activity (EC 4.3.1.5), protein and antioxidant activity (FRAP) of [...] Read more.
A split plot 3 by 3 experiment was designed to investigate the relationships among production of primary metabolites (soluble sugar and starch), secondary metabolites (total flavonoids, TF; total phenolics, TP), phenylalanine lyase (PAL) activity (EC 4.3.1.5), protein and antioxidant activity (FRAP) of three progenies of oil palm seedlings, namely Deli AVROS, Deli Yangambi and Deli URT, under three levels of CO2 enrichment (400, 800 and 1,200 µmol·mol−1) for 15 weeks of exposure. During the study, the treatment effects were solely contributed by CO2 enrichment levels; no progenies and interaction effects were observed. As CO2 levels increased from 400 to 1,200 µmol·mol−1, the production of carbohydrate increased steadily, especially for starch more than soluble sugar. The production of total flavonoids and phenolics contents, were the highest under 1,200 and lowest at 400 µmol·mol−1. It was found that PAL activity was peaked under 1,200 µmol·mol−1 followed by 800 µmol·mol−1 and 400 µmol·mol−1. However, soluble protein was highest under 400 µmol·mol−1 and lowest under 1,200 µmol·mol−1. The sucrose/starch ratio, i.e., the indication of sucrose phosphate synthase actvity (EC 2.4.1.14) was found to be lowest as CO2 concentration increased from 400 > 800 > 1,200 µmol·mol−1. The antioxidant activity, as determined by the ferric reducing/antioxidant potential (FRAP) activity, increased with increasing CO2 levels, and was significantly lower than vitamin C and α-tocopherol but higher than butylated hydroxytoluene (BHT). Correlation analysis revealed that nitrogen has a significant negative correlation with carbohydrate, secondary metabolites and FRAP activity indicating up-regulation of production of carbohydrate, secondary metabolites and antioxidant activity of oil palm seedling under elevated CO2 was due to reduction in nitrogen content in oil palm seedling expose to high CO2 levels. Full article
Open AccessArticle Benzyl 2-β-Glucopyranosyloxybenzoate, a New Phenolic Acid Glycoside from Sarcandra glabra
Molecules 2012, 17(5), 5212-5218; doi:10.3390/molecules17055212
Received: 13 April 2012 / Revised: 23 April 2012 / Accepted: 23 April 2012 / Published: 4 May 2012
Cited by 2 | PDF Full-text (264 KB)
Abstract
From the whole plant of Sarcandra glabra, a new phenolic acid glycoside, benzyl 2-β-glucopyranosyloxybenzoate (1), together with seven known compounds including eleutheroside B1 (2), 5-O-caffeoylshikimic acid (3), (–)-(7S, 8R [...] Read more.
From the whole plant of Sarcandra glabra, a new phenolic acid glycoside, benzyl 2-β-glucopyranosyloxybenzoate (1), together with seven known compounds including eleutheroside B1 (2), 5-O-caffeoylshikimic acid (3), (–)-(7S, 8R)-dihydrodehydro-diconiferyl alcohol (4), (–)-(7S, 8R)-dihydrodehydrodiconiferyl alcohol 9-, 9′- and 4-O-â-D-glucopyranoside (57), and (–)-(7S, 8R)-5-methoxydihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside (8) was isolated. Their structures were elucidated by spectral analysis including 1D-, 2D-NMR and HR-ESI-MS. Compound 2 was found to exhibit potent cytotoxic activity against BGC-823 and A2780 cancer cell lines using MTT method with IC50 value of 2.53 and 1.85 µM, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Phaeophytin Analogues from Ligularia knorringiana
Molecules 2012, 17(5), 5219-5224; doi:10.3390/molecules17055219
Received: 15 March 2012 / Revised: 25 April 2012 / Accepted: 27 April 2012 / Published: 7 May 2012
PDF Full-text (206 KB) | Supplementary Files
Abstract
A new phaeophytin, ligulariaphytin A, together with five known phaeophytins, were isolated from the aerial parts of Ligularia knorringiana. The structure of ligulariaphytin A was elucidated as 131-hydroxy-131,132-peroxyphaeophorbide A ethyl ester (1), and [...] Read more.
A new phaeophytin, ligulariaphytin A, together with five known phaeophytins, were isolated from the aerial parts of Ligularia knorringiana. The structure of ligulariaphytin A was elucidated as 131-hydroxy-131,132-peroxyphaeophorbide A ethyl ester (1), and the five known compounds were identified as 132-hydroxyphaeophorbide A ethyl ester (2), 173-ethoxyphaeophorbide A (3), phaeophytin B (4), phaeophytin A (5), and phaeophorbide B ethyl ester (6), respectively, based on spectroscopic analysis and by comparison of their spectral data with those reported previously in the literature. All compounds were evaluated for their in vitro cytotoxic activities against cultured Hela cell, and were found to show only very weak cytotoxicity. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis and Characterization of Positively Charged Pentacationic [60]Fullerene Monoadducts for Antimicrobial Photodynamic Inactivation
Molecules 2012, 17(5), 5225-5243; doi:10.3390/molecules17055225
Received: 31 March 2012 / Revised: 22 April 2012 / Accepted: 28 April 2012 / Published: 7 May 2012
Cited by 8 | PDF Full-text (476 KB) | Supplementary Files
Abstract
We designed and synthesized two analogous pentacationic [60]fullerenyl monoadducts, C60(>ME1N6+C3) (1) and C60(>ME3N6+C3) (2), with variation of the methoxyethyleneglycol length. [...] Read more.
We designed and synthesized two analogous pentacationic [60]fullerenyl monoadducts, C60(>ME1N6+C3) (1) and C60(>ME3N6+C3) (2), with variation of the methoxyethyleneglycol length. Each of these derivatives bears a well-defined number of cationic charges aimed to enhance and control their ability to target pathogenic Gram-positive and Gram-negative bacterial cells for allowing photodynamic inactivation. The synthesis was achieved by the use of a common synthon of pentacationic N,N′,N,N,N,N-hexapropyl-hexa(aminoethyl)amine arm (C3N6+) having six attached propyl groups, instead of methyl or ethyl groups, to provide a well-balanced hydrophobicity–hydrophilicity character to pentacationic precursor intermediates and better compatibility with the highly hydrophobic C60 cage moiety. We demonstrated two plausible synthetic routes for the preparation of 1 and 2 with the product characterization via various spectroscopic methods. Full article
(This article belongs to the Special Issue Fullerene Chemistry)
Open AccessArticle Lectin from Canavalia brasiliensis Seeds (ConBr) Is a Valuable Biotechnological Tool to Stimulate the Growth of Rhizobium tropici in Vitro
Molecules 2012, 17(5), 5244-5254; doi:10.3390/molecules17055244
Received: 5 April 2012 / Revised: 22 April 2012 / Accepted: 25 April 2012 / Published: 7 May 2012
Cited by 6 | PDF Full-text (480 KB)
Abstract
To study the interactions between a Rhizobium tropici strain and lectins isolated from the seeds of Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr), a lectin fluorescence assay was performed. In addition, an experiment was designed to evaluate the effect of the two [...] Read more.
To study the interactions between a Rhizobium tropici strain and lectins isolated from the seeds of Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr), a lectin fluorescence assay was performed. In addition, an experiment was designed to evaluate the effect of the two lectins on bacterial growth. Both lectins were found to bind to R. tropici cells, but the interactions were inhibited by D-mannose. Interestingly, only ConBr stimulated bacterial growth in proportion to the concentrations used (15.6–500 µg/mL), and the bacterial growth stimulation was inhibited by D-mannose as well. Structure/Function analyses by bioinformatics were carried out to evaluate the volume and carbohydrate recognition domain (CRD) configuration of ConA and ConBr. The difference of spatial arrangement and volume of CRD may indicate the variation between biological activities of both lectins. The results suggest that ConBr could be a promising tool for studies focusing on the interactions between rhizobia and host plants. Full article
Open AccessArticle Mutagenicity of Flavonoids Assayed by Bacterial Reverse Mutation (Ames) Test
Molecules 2012, 17(5), 5255-5268; doi:10.3390/molecules17055255
Received: 13 April 2012 / Revised: 25 April 2012 / Accepted: 27 April 2012 / Published: 7 May 2012
Cited by 29 | PDF Full-text (219 KB)
Abstract
The mutagenicity of ten flavonoids was assayed by the Ames test, in Salmonella typhimurium strains TA98, TA100 and TA102, with the aim of establishing hydroxylation pattern-mutagenicity relationship profiles. The compounds assessed were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and [...] Read more.
The mutagenicity of ten flavonoids was assayed by the Ames test, in Salmonella typhimurium strains TA98, TA100 and TA102, with the aim of establishing hydroxylation pattern-mutagenicity relationship profiles. The compounds assessed were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone. In the Ames assay, quercetin acted directly and its mutagenicity increased with metabolic activation. In the presence of S9 mix, kaempferol and galangin were mutagenic in the TA98 strain and kaempferol showed signs of mutagenicity in the other strains. The absence of hydroxyl groups, as in flavone, only signs of mutagenicity were shown in strain TA102, after metabolization and, among monohydroxylated flavones (3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone), the presence of hydroxyl groups only resulted in minor changes. Luteolin and fisetin also showed signs of mutagenicity in strain TA102. Finally, chrysin, which has only two hydroxy groups, at the 5-OH and 7-OH positions, also did not induce mutagenic activity in any of the bacterial strains used, under either activation condition. All the flavonoids were tested at concentrations varying from 2.6 to 30.7 nmol/plate for galangin and 12.1 to 225.0 nmol/plate for other flavonoids. In light of the above, it is necessary to clarify the conditions and the mechanisms that mediate the biological effects of flavonoids before treating them as therapeutical agents, since some compounds can be biotransformed into more genotoxic products; as is the case for galangin, kaempferol and quercetin. Full article
(This article belongs to the collection Bioactive Compounds)
Open AccessArticle Kale Extract Increases Glutathione Levels in V79 Cells, but Does not Protect Them against Acute Toxicity Induced by Hydrogen Peroxide
Molecules 2012, 17(5), 5269-5288; doi:10.3390/molecules17055269
Received: 9 April 2012 / Revised: 24 April 2012 / Accepted: 25 April 2012 / Published: 7 May 2012
Cited by 4 | PDF Full-text (360 KB)
Abstract
This study aims to evaluate the antioxidant potential of extracts of Brassica oleracea L. var. acephala DC. (kale) and several materials of Pieris brassicae L., a common pest of Brassica cultures using a cellular model with hamster lung fibroblast (V79 cells) under [...] Read more.
This study aims to evaluate the antioxidant potential of extracts of Brassica oleracea L. var. acephala DC. (kale) and several materials of Pieris brassicae L., a common pest of Brassica cultures using a cellular model with hamster lung fibroblast (V79 cells) under quiescent conditions and subjected to H2O2-induced oxidative stress. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and glutathione was determined by the 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)-oxidized glutathione (GSSG) reductase recycling assay. The phenolic composition of the extracts was also established by HPLC-DAD. They presented acylated and non acylated flavonoid glycosides, some of them sulfated, and hydroxycinnamic acyl gentiobiosides. All extracts were cytotoxic by themselves at high concentrations and failed to protect V79 cells against H2O2 acute toxicity. No relationship between phenolic composition and cytotoxicity of the extracts was found. Rather, a significant increase in glutathione was observed in cells exposed to kale extract, which contained the highest amount and variety of flavonoids. It can be concluded that although flavonoids-rich extracts have the ability to increase cellular antioxidant defenses, the use of extracts of kale and P. brassicae materials by pharmaceutical or food industries, may constitute an insult to health, especially to debilitated individuals, if high doses are consumed. Full article
Open AccessArticle Molluscicidal Activity of Methomyl and Cardenolide Extracts from Calotropis procera and Adenium arabicum Against the Land Snail Monacha cantiana
Molecules 2012, 17(5), 5310-5318; doi:10.3390/molecules17055310
Received: 26 March 2012 / Revised: 28 April 2012 / Accepted: 28 April 2012 / Published: 7 May 2012
Cited by 4 | PDF Full-text (276 KB)
Abstract
In this work, we have evaluated the molluscicidal activity of two cardenolide extracts from Adenium arabicum Balf f. [the benzene (B) and methanol (M) extracts], one cardenolide extract from Calotropis procera (Aiton) W.T. Aiton (extract C), and methomyl against the harmful land [...] Read more.
In this work, we have evaluated the molluscicidal activity of two cardenolide extracts from Adenium arabicum Balf f. [the benzene (B) and methanol (M) extracts], one cardenolide extract from Calotropis procera (Aiton) W.T. Aiton (extract C), and methomyl against the harmful land snail Monacha cantiana (Montagu). The contact LD50 values for the above mentioned plant extracts were 12.62, 34.63, and 34.35 mg·kg−1 of body weight, respectively, while the LD50 for methomyl was 116.62 mg·kg−1, that is, the plant extracts were 9.24, 3.37, and 3.4 times more toxic than methomyl. In addition, a simple colorimetric method, based on Kedde reagent, was modified to determine cardenolide concentrations in plant extracts. Thin layer chromatography analysis (TLC) showed several cardiac glycosidal compounds in each plant extract. The results proved that cardiac glycosides are promising candidate compounds that could be used to control land snails, or exploited to develop new, effective, and environmentally friendly molluscicides. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A Convenient Synthesis of Triflate Anion Ionic Liquids and Their Properties
Molecules 2012, 17(5), 5319-5338; doi:10.3390/molecules17055319
Received: 7 March 2012 / Revised: 13 April 2012 / Accepted: 13 April 2012 / Published: 7 May 2012
Cited by 13 | PDF Full-text (355 KB)
Abstract
A solvent- and halogen-free synthesis of high purity triflate ionic liquids via direct alkylation of organic bases (amines, phosphines or heterocyclic compounds) with methyl and ethyl trifluoromethanesulfonate (methyl and ethyl triflate) has been developed. Cheap and non-toxic dimethyl and diethyl carbonate serve [...] Read more.
A solvent- and halogen-free synthesis of high purity triflate ionic liquids via direct alkylation of organic bases (amines, phosphines or heterocyclic compounds) with methyl and ethyl trifluoromethanesulfonate (methyl and ethyl triflate) has been developed. Cheap and non-toxic dimethyl and diethyl carbonate serve as source for the methyl and ethyl groups in the preparation of methyl and ethyl triflate by this invented process. The properties of ionic liquids containing the triflate anion are determined and discussed. Full article
(This article belongs to the Special Issue Ionic Liquids)
Open AccessCommunication Synthesis of N-substituted Acridinediones and Polyhydroquinoline Derivatives in Refluxing Water
Molecules 2012, 17(5), 5339-5345; doi:10.3390/molecules17055339
Received: 13 March 2012 / Revised: 24 April 2012 / Accepted: 28 April 2012 / Published: 7 May 2012
Cited by 13 | PDF Full-text (177 KB) | Supplementary Files
Abstract
Acridinediones were synthesized by the one-pot Hantzsch condensation of an aromatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione, and aniline/4-methylaniline in refluxing water. This method has then been extended to the four-component reaction of an aromatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione, ethyl acetoacetate and ammonium acetate for the synthesis of [...] Read more.
Acridinediones were synthesized by the one-pot Hantzsch condensation of an aromatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione, and aniline/4-methylaniline in refluxing water. This method has then been extended to the four-component reaction of an aromatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione, ethyl acetoacetate and ammonium acetate for the synthesis of polyhydroquinoline derivatives. This is an environmentally friendly and efficient procedure providing good to excellent yields. Full article
Open AccessArticle Parallel Synthesis of Peptide-Like Macrocycles Containing Imidazole-4,5-dicarboxylic Acid
Molecules 2012, 17(5), 5346-5362; doi:10.3390/molecules17055346
Received: 5 April 2012 / Revised: 26 April 2012 / Accepted: 3 May 2012 / Published: 8 May 2012
Cited by 2 | PDF Full-text (741 KB) | Supplementary Files
Abstract
We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles [...] Read more.
We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles retain some level of conformational variability as observed by both molecular modeling and X-ray crystallography. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets. Full article
(This article belongs to the Special Issue Parallel Synthesis)
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Open AccessArticle Parallel Synthesis of 2-Substituted 6-(5-Oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides
Molecules 2012, 17(5), 5363-5384; doi:10.3390/molecules17055363
Received: 20 March 2012 / Revised: 24 April 2012 / Accepted: 26 April 2012 / Published: 8 May 2012
Cited by 4 | PDF Full-text (343 KB)
Abstract
A library of 24 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides 10{1,2; 1–12} was prepared by a parallel solution-phase approach. The synthesis comprises a five-step transformation of itaconic acid (11) into 1-methyl and 1-phenyl substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxylic acids 17{1 [...] Read more.
A library of 24 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides 10{1,2; 1–12} was prepared by a parallel solution-phase approach. The synthesis comprises a five-step transformation of itaconic acid (11) into 1-methyl and 1-phenyl substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxylic acids 17{1,2} followed by parallel amidation of 17{1,2} with a series of 12 aliphatic amines 18{1–12} to afford the corresponding carboxamides 10 in good overall yields and in 80–100% purity. Full article
(This article belongs to the Special Issue Parallel Synthesis)
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Open AccessArticle Free Radical Scavenging, Antimicrobial and Immunomodulatory Activities of Orthosiphon stamineus
Molecules 2012, 17(5), 5385-5395; doi:10.3390/molecules17055385
Received: 12 March 2012 / Revised: 10 April 2012 / Accepted: 17 April 2012 / Published: 8 May 2012
Cited by 10 | PDF Full-text (279 KB)
Abstract
Orthosiphon stamineus is considered an important traditional folk medicine. In this study ethanol and aqueous extracts of O. stamineus were evaluated in vitro for their antioxidant, antimicrobial as well as for their immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). The [...] Read more.
Orthosiphon stamineus is considered an important traditional folk medicine. In this study ethanol and aqueous extracts of O. stamineus were evaluated in vitro for their antioxidant, antimicrobial as well as for their immunomodulatory properties on human peripheral blood mononuclear cells (PBMCs). The DPPH radical scavenging method was used for the determination of antioxidant activity, while the antibacterial efficacy was investigated by both disc diffusion method and Minimum Inhibitory Concentration (MIC) against four bacterial strains (Gram-positive and Gram-negative). Furthermore, the immunomodulatory potential of the extracts was investigated through the MTT assay. Aqueous extract of O. stamineus exhibited significant free radical scavenging activity with IC50 9.6 µg/mL, whereas the IC50 for the ethanol extract was 21.4 µg/mL. The best antimicrobial activity was shown by the aqueous extract of O. stamineus against Staphylococcus aureus, with inhibition zone of 10.5 mm and MIC value 1.56 mg/mL. Moreover, the results observed from the MTT assay showed that both plant extracts stimulated the PBMCs proliferation in vitro in a concentration-dependent manner, but the aqueous extract has remarkable activity against PBMCs. These findings indicate that O. stamineus showed high antioxidant activity and may be considered as an immunomodulatory agent. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Two New Cyanogenic Glucosides from the Leaves of Hydrangea macrophylla
Molecules 2012, 17(5), 5396-5403; doi:10.3390/molecules17055396
Received: 27 March 2012 / Revised: 22 April 2012 / Accepted: 27 April 2012 / Published: 8 May 2012
Cited by 2 | PDF Full-text (237 KB)
Abstract
Chemical investigation of the ethanol extract of the aerial parts of Hydrangea macrophylla collected in the Sichuan Province of China resulted in the isolation of two new cyanogenic glucosides. Their structures were elucidated as [(2R)-2-(b-D-glucopyranosyloxy)-2-(3,4-dimethoxy-phenyl)] acetonitrile (1 [...] Read more.
Chemical investigation of the ethanol extract of the aerial parts of Hydrangea macrophylla collected in the Sichuan Province of China resulted in the isolation of two new cyanogenic glucosides. Their structures were elucidated as [(2R)-2-(b-D-glucopyranosyloxy)-2-(3,4-dimethoxy-phenyl)] acetonitrile (1) and {(2R)-2-[a-D-glucopyranosyl(1®6)b-D-glucopyranosyloxy]-2-(3-hydroxy-4-methoxy-phenyl)}acetonitrile (2) on the basis of extensive spectroscopic analysis (1D, 2D NMR and HRESIMS) and chemical studies. Full article
Open AccessCommunication Immunostimulatory Effect of Laminarin on RAW 264.7 Mouse Macrophages
Molecules 2012, 17(5), 5404-5411; doi:10.3390/molecules17055404
Received: 1 March 2012 / Revised: 25 April 2012 / Accepted: 3 May 2012 / Published: 8 May 2012
Cited by 14 | PDF Full-text (843 KB)
Abstract
This study investigated the immunostimulatory effects of laminarin with respect to inflammatory mediators such as hydrogen peroxide, calcium, nitric oxide, various cytokines, transcription factors, and immune response gene in RAW 264.7 mouse macrophages. Laminarin did not reduce the cell proliferation of RAW [...] Read more.
This study investigated the immunostimulatory effects of laminarin with respect to inflammatory mediators such as hydrogen peroxide, calcium, nitric oxide, various cytokines, transcription factors, and immune response gene in RAW 264.7 mouse macrophages. Laminarin did not reduce the cell proliferation of RAW 264.7 mouse macrophages at concentrations up to 500 µg/mL. Laminarin significantly increased the release of hydrogen peroxide, calcium, nitric oxide, monocyte chemotactic protein-1, vascular endothelial growth factor, leukemia inhibitory factor, and granulocyte-colony stimulating factor with enhancing expression of Signal Transducer and Activator of Transcription 1 (STAT1), STAT3, c-Jun, c-Fos, and cyclooxygenase-2 mRNA in RAW 264.7 cells. The results suggest that laminarin has immunostimulatory properties, strengthening immune reactions via the transcription factor pathway in macrophages. Full article
(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)
Open AccessArticle Evaluation of Antioxidant and Immunity Function of Tetramethylpyrazine Phosphate Tablets in Vivo
Molecules 2012, 17(5), 5412-5421; doi:10.3390/molecules17055412
Received: 16 April 2012 / Revised: 28 April 2012 / Accepted: 28 April 2012 / Published: 8 May 2012
Cited by 8 | PDF Full-text (179 KB)
Abstract
The aim of the study was to determine the effect of tetramethylpyrazine phosphate tablets (TPT), a Chinese medicine used for cardiovascular disease, on immunity activity and oxidative injury in rats. Heart failure (HF) was induced by isoproterenol (ISO). After the animal model [...] Read more.
The aim of the study was to determine the effect of tetramethylpyrazine phosphate tablets (TPT), a Chinese medicine used for cardiovascular disease, on immunity activity and oxidative injury in rats. Heart failure (HF) was induced by isoproterenol (ISO). After the animal model was established, the rats were administered the TPT by gavage (once a day). The results indicated that TPT improved left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dP/dt, heart weight/body weight. TPT could decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Furthermore, it also could raise the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but reduce malonyldialdehyde (MDA) level. The results indicated that TPT improved cardiac function and myocardial fibrosis from myocardial injury, and this cardioprotection might be attributed to a reduction of oxidative stress and regulation of inflammation mediators. Full article
Open AccessArticle Two New Cembrane-Based Diterpenoids from the Marine Soft Coral Sinularia crassa
Molecules 2012, 17(5), 5422-5429; doi:10.3390/molecules17055422
Received: 10 January 2012 / Revised: 4 May 2012 / Accepted: 8 May 2012 / Published: 8 May 2012
Cited by 10 | PDF Full-text (311 KB) | Supplementary Files
Abstract
Two new cembrane diterpenes, sicrassarines A and B (compounds 1 and 2), were isolated from the Taiwanese soft coral Sinularia crassa. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and [...] Read more.
Two new cembrane diterpenes, sicrassarines A and B (compounds 1 and 2), were isolated from the Taiwanese soft coral Sinularia crassa. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy. Full article
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Open AccessArticle Evaluation of Antioxidant Activities of Aqueous Extracts and Fractionation of Different Parts of Elsholtzia ciliata
Molecules 2012, 17(5), 5430-5441; doi:10.3390/molecules17055430
Received: 17 April 2012 / Revised: 25 April 2012 / Accepted: 28 April 2012 / Published: 9 May 2012
Cited by 10 | PDF Full-text (490 KB)
Abstract
The aim of this study was to investigate the antioxidant and free-radical scavenging activity of extract and fractions from various parts of Elsholtzia ciliata. The inflorescences, leaves, stems and roots of E. ciliata were extracted separately and two phenolic component enrichment [...] Read more.
The aim of this study was to investigate the antioxidant and free-radical scavenging activity of extract and fractions from various parts of Elsholtzia ciliata. The inflorescences, leaves, stems and roots of E. ciliata were extracted separately and two phenolic component enrichment methods: ethyl acetate-water liquid-liquid extraction and macroporous resin adsorption-desorption, were adopted in this study. The antioxidant activities of water extracts and fractions of E. ciliata were examined using different assay model systems in vitro. The fraction root E (purified by HPD300 macroporous resin) exhibited the highest total phenolics content (497.2 ± 24.9 mg GAE/g), accompanied with the highest antioxidant activity against various antioxidant systems in vitro compared to other fractions. On the basis of the results obtained, E. ciliata extracts can be used potentially as a ready accessible and valuable bioactive source of natural antioxidants. Full article
Open AccessArticle FG020326 Sensitized Multidrug Resistant Cancer Cells to Docetaxel-Mediated Apoptosis via Enhancement of Caspases Activation
Molecules 2012, 17(5), 5442-5458; doi:10.3390/molecules17055442
Received: 13 March 2012 / Revised: 21 April 2012 / Accepted: 28 April 2012 / Published: 9 May 2012
Cited by 3 | PDF Full-text (1585 KB)
Abstract
Apoptotic resistance is the main obstacle for treating cancer patients with chemotherapeutic drugs. Multidrug resistance (MDR) is often characterized by the expression of P-glycoprotein (P-gp), a 170-KD ATP-dependent drug efflux protein. Functional P-gp can confer resistance to activate caspase-8 and -3 dependent [...] Read more.
Apoptotic resistance is the main obstacle for treating cancer patients with chemotherapeutic drugs. Multidrug resistance (MDR) is often characterized by the expression of P-glycoprotein (P-gp), a 170-KD ATP-dependent drug efflux protein. Functional P-gp can confer resistance to activate caspase-8 and -3 dependent apoptosis induced by a range of different stimuli, including tumor necrosis and chemotherapeutic drugs such as docetaxel and vincristine. We demonstrated here that comparison of sensitive KB cells, P-gp positive (P-gp+ve) KBv200 cells were extremely resistant to apoptosis induced by docetaxel. FG020326, a pharmacological inhibitor of P-gp function, could enhance concentration-dependently the effect of docetaxel on cell apoptosis and sensitize caspase-8, -9 and -3 activation in P-gp overexpressing KBv200 cells, but not in KB cells. Therefore, the enhancement of caspase-8, -9 and -3 activation induced by docetaxel may be one of the key mechanisms of the reversal of P-gp mediated docetaxel resistance by FG020326. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Isolation and Characterization of Phenolic Antioxidants from Plantago Herb
Molecules 2012, 17(5), 5459-5466; doi:10.3390/molecules17055459
Received: 12 April 2012 / Revised: 2 May 2012 / Accepted: 4 May 2012 / Published: 9 May 2012
Cited by 6 | PDF Full-text (287 KB) | Supplementary Files
Abstract
Seven phenolic compounds, including a new phenylethanoid glycoside, were isolated from the ethyl acetate fraction of an aqueous ethanol extract of Plantago Herb (whole part of Plantago asiatica L.), which showed significant antioxidative activity. The new compound was characterized as 2-(3,4-dihydroxyphenyl)ethyl 3- [...] Read more.
Seven phenolic compounds, including a new phenylethanoid glycoside, were isolated from the ethyl acetate fraction of an aqueous ethanol extract of Plantago Herb (whole part of Plantago asiatica L.), which showed significant antioxidative activity. The new compound was characterized as 2-(3,4-dihydroxyphenyl)ethyl 3-O-β-D-allopyranosyl-6-O-caffeoyl-β-D-glucopyranoside on the basis of spectral and chemical evidence, and its antioxidant activity was comparable to that of tea catechins. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Quinoline-3-carboxamide Derivatives as Potential Cholesteryl Ester Transfer Protein Inhibitors
Molecules 2012, 17(5), 5497-5507; doi:10.3390/molecules17055497
Received: 26 March 2012 / Revised: 14 April 2012 / Accepted: 20 April 2012 / Published: 9 May 2012
Cited by 3 | PDF Full-text (248 KB)
Abstract
A series of novel quinoline-3-carboxamide derivatives 1017 and 2327 were designed and synthesized as cholesteryl ester transfer protein (CETP) inhibitors. All of them exhibited activity against CETP. Particularly, compounds 24 and 26 displayed the best activity against CETP [...] Read more.
A series of novel quinoline-3-carboxamide derivatives 1017 and 2327 were designed and synthesized as cholesteryl ester transfer protein (CETP) inhibitors. All of them exhibited activity against CETP. Particularly, compounds 24 and 26 displayed the best activity against CETP with the same inhibitory rate of 80.1%. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle H2TPP Organocatalysis in Mild and Highly Regioselective Ring Opening of Epoxides to Halo Alcohols by Means of Halogen Elements
Molecules 2012, 17(5), 5508-5519; doi:10.3390/molecules17055508
Received: 10 January 2012 / Revised: 6 April 2012 / Accepted: 12 April 2012 / Published: 9 May 2012
Cited by 1 | PDF Full-text (375 KB)
Abstract
We found that elemental iodine and bromine are converted to trihalide nucleophiles (triiodine and tribromide anion, respectively) in the presence of catalytic amounts of meso-tetraphenylporphyrins (H2TPP). Therefore a highly regioselective method for the synthesis of b-haloalcohols through direct ring [...] Read more.
We found that elemental iodine and bromine are converted to trihalide nucleophiles (triiodine and tribromide anion, respectively) in the presence of catalytic amounts of meso-tetraphenylporphyrins (H2TPP). Therefore a highly regioselective method for the synthesis of b-haloalcohols through direct ring opening of epoxides with elemental iodine and bromine in the presence of H2TPPs as new catalysts is described. At room temperature a series of epoxide derivatives were converted into the corresponding halohydrins resulting from an attack of trihalide species anion atoms at the less substituted carbon atom. This method occurs under neutral and mild conditions with high yields in various aprotic solvents, even when sensitive functional groups are present. Full article
(This article belongs to the Special Issue Organocatalysis)
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Open AccessArticle Saponins with Neuroprotective Effects from the Roots of Pulsatilla cernua
Molecules 2012, 17(5), 5520-5531; doi:10.3390/molecules17055520
Received: 1 April 2012 / Revised: 3 May 2012 / Accepted: 4 May 2012 / Published: 9 May 2012
Cited by 13 | PDF Full-text (313 KB) | Supplementary Files
Abstract
Four new oleanene-type triterpenoid saponins together with six known saponins were isolated from the roots of Pulsatilla cernua and their structures were elucidated on the basis of spectroscopic data, including 2D NMR spectra and chemical evidence. Among these one of the [...] Read more.
Four new oleanene-type triterpenoid saponins together with six known saponins were isolated from the roots of Pulsatilla cernua and their structures were elucidated on the basis of spectroscopic data, including 2D NMR spectra and chemical evidence. Among these one of the aglycones (gypsogenin) is reported for the first time from this genus. Some of these compounds showed significant neuroprotective effects against the cytotoxicity induced by β-amyloid25–35 (Aβ25–35) on human neuroblastoma SH-SY5Y cells. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Synthesis and Characterization of Triphenylphosphine Adducts of Ferrocene-Based Palladacycles and Their Performance in the Suzuki and Sonogashira Reactions with Bromo- and Chloroarenes
Molecules 2012, 17(5), 5532-5543; doi:10.3390/molecules17055532
Received: 12 April 2012 / Revised: 3 May 2012 / Accepted: 4 May 2012 / Published: 9 May 2012
Cited by 2 | PDF Full-text (458 KB)
Abstract
A new triphenylphosphine adduct of cyclopalladated ferrocenylpyridazine containing a chloride anion, 2a, has been synthesized from the reaction of the chloride-bridged palladacyclic dimer 1a with triphenylphosphine. The corresponding adducts 3a,b containing iodide anion have been readily prepared [...] Read more.
A new triphenylphosphine adduct of cyclopalladated ferrocenylpyridazine containing a chloride anion, 2a, has been synthesized from the reaction of the chloride-bridged palladacyclic dimer 1a with triphenylphosphine. The corresponding adducts 3a,b containing iodide anion have been readily prepared through anion exchange reactions of 2a,b with NaI in acetone. These complexes were characterized by elemental analysis, IR and 1H-NMR. Additionally, their crystal structures have been determined by X-ray diffraction and intermolecular C–H···X (Cl, Br, I) bonds were found in the crystals. The use of these palladacycles as catalysts for the Suzuki and Sonogashira reactions was examined. The complexes 2a,b exhibited higher catalytic activity than the corresponding 3a,b in the Suzuki reaction. However, the order of activity of adducts with varying halogen anions is 3a~3b > 2a~2b in the Sonogashira reaction. Full article
Open AccessArticle Two New Aryltetralin Lignans from the Roots of Dolomiaea souliei
Molecules 2012, 17(5), 5544-5549; doi:10.3390/molecules17055544
Received: 9 April 2012 / Revised: 26 April 2012 / Accepted: 27 April 2012 / Published: 9 May 2012
Cited by 3 | PDF Full-text (198 KB)
Abstract
Two new aryltetralin-type lignans, dolomiaeasin A (1) and dolomiaeasin B (2), were isolated from the roots of Dolomiaea souliei. Their structures were elucidated by means of various spectroscopic analyses. The cytotoxicities of 1 and 2 were tested [...] Read more.
Two new aryltetralin-type lignans, dolomiaeasin A (1) and dolomiaeasin B (2), were isolated from the roots of Dolomiaea souliei. Their structures were elucidated by means of various spectroscopic analyses. The cytotoxicities of 1 and 2 were tested by the MTT method, and both compounds showed no significant cytotoxic activities against the A549 and A2780 human cancer cell lines. This is the first time that aryltetralin-type lignans were isolated from the genus Dolomiaea. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Synthesis and Characterization of Some New C2 Symmetric Chiral Bisamide Ligands Derived from Chiral Feist’s Acid
Molecules 2012, 17(5), 5550-5563; doi:10.3390/molecules17055550
Received: 7 February 2012 / Revised: 16 April 2012 / Accepted: 20 April 2012 / Published: 9 May 2012
Cited by 1 | PDF Full-text (323 KB) | Supplementary Files
Abstract
The hemilabile chiral C2 symmetrical bidentate substituted amide ligands (1R,2R)-5a-d and (1S,2S)-6a-d were synthesized in quantitative yield from (1R,2R)-(+)-3-methylenecyclo-propane-1,2-dicarboxylic acid (1R,2R)- [...] Read more.
The hemilabile chiral C2 symmetrical bidentate substituted amide ligands (1R,2R)-5a-d and (1S,2S)-6a-d were synthesized in quantitative yield from (1R,2R)-(+)-3-methylenecyclo-propane-1,2-dicarboxylic acid (1R,2R)-3 and (1S,2S)-(-)-3-methylene-cyclopropane-1,2-dicarboxylic acid (1S,2S)-3, in two steps, respectively. The chiral Feist’s acids (1R,2R)-3 and (1S,2S)-3 were obtained in good isomeric purity by resolution of trans-(±)-3-methylene-cyclopropane-1,2-dicarboxylic acid from an 8:2 mixture of tert-butanol and water, using (R)-(+)-α-methylbenzyl amine as a chiral reagent. This process is reproducible on a large scale. All these new synthesized chiral ligands were characterized by 1H-NMR, 13C-NMR, IR, and mass spectrometry, as well as elemental analysis and their specific rotations were measured. These new classes of C2 symmetric chiral bisamide ligands could be of special interest in asymmetric transformations. Full article
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Open AccessArticle Microwave Synthesis Under Solvent-Free Conditions and Spectral Studies of Some Mesoporphyrinic Complexes
Molecules 2012, 17(5), 5592-5603; doi:10.3390/molecules17055592
Received: 20 March 2012 / Revised: 4 May 2012 / Accepted: 7 May 2012 / Published: 10 May 2012
Cited by 5 | PDF Full-text (220 KB)
Abstract
A series of A3B and A4 type mesoporphyrinic complexes were synthesized with superior yields using microwave irradiation under solvent-free conditions. The structures of the complexes were confirmed using elemental analysis, FT-IR, UV-Vis, EPR and NMR spectral data. The influence [...] Read more.
A series of A3B and A4 type mesoporphyrinic complexes were synthesized with superior yields using microwave irradiation under solvent-free conditions. The structures of the complexes were confirmed using elemental analysis, FT-IR, UV-Vis, EPR and NMR spectral data. The influence of environmental polarity on spectral properties of the mesoporphyrinic complexes was investigated. The obtained results indicate that the shape of absorption and fluorescence spectra does not depend on the solvent polarity under the experimental conditions used. The small shifts of the absorption and emission maximums that occur by increasing of solvent polarity reflects the physical interaction between the porphyrinic substituents and the solvent molecules. Full article
(This article belongs to the Special Issue Solvent-Free Synthesis)
Open AccessArticle Novel Synthesis of 8-Deaza-5,6,7,8-tetrahydroaminopterin Analogues via an Aziridine Intermediate
Molecules 2012, 17(5), 5604-5614; doi:10.3390/molecules17055604
Received: 10 April 2012 / Revised: 3 May 2012 / Accepted: 5 May 2012 / Published: 10 May 2012
PDF Full-text (307 KB)
Abstract
An efficient method for the construction of the tetrahydrofolate skeleton is described. Starting from pterin analogues and aromatic amines, 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives and the heterocyclic benzoyl isosteres were synthesized via a novel aziridine intermediate. Following this method, the byproducts of carbon-nitrogen bond hydrogenolysis [...] Read more.
An efficient method for the construction of the tetrahydrofolate skeleton is described. Starting from pterin analogues and aromatic amines, 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives and the heterocyclic benzoyl isosteres were synthesized via a novel aziridine intermediate. Following this method, the byproducts of carbon-nitrogen bond hydrogenolysis in traditional synthetic strategy can be completely avoided. Full article
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Open AccessArticle Chiral Aminophosphines as Catalysts for Enantioselective Double-Michael Indoline Syntheses
Molecules 2012, 17(5), 5626-5650; doi:10.3390/molecules17055626
Received: 23 March 2012 / Revised: 19 April 2012 / Accepted: 23 April 2012 / Published: 11 May 2012
Cited by 7 | PDF Full-text (638 KB)
Abstract
The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient acetylenes is an efficient process for the synthesis of many nitrogen-containing heterocycles. Because the resulting heterocycles contain at least one stereogenic center, this double-Michael reaction would be even more useful if an asymmetric variant [...] Read more.
The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient acetylenes is an efficient process for the synthesis of many nitrogen-containing heterocycles. Because the resulting heterocycles contain at least one stereogenic center, this double-Michael reaction would be even more useful if an asymmetric variant of the reaction were to be developed. Aminophosphines can also facilitate the double-Michael reaction and chiral amines are more readily available in Nature and synthetically; therefore, in this study we prepared several new chiral aminophosphines. When employed in the asymmetric double-Michael reaction between ortho-tosylamidophenyl malonate and 3-butyn-2-one, the chiral aminophosphines produced indolines in excellent yields with moderate asymmetric induction. Full article
(This article belongs to the Special Issue Asymmetric Catalysis)
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Open AccessArticle Stability of Carotenoid Diets During Feed Processing and Under Different Storage Conditions
Molecules 2012, 17(5), 5651-5660; doi:10.3390/molecules17055651
Received: 7 February 2012 / Revised: 4 May 2012 / Accepted: 8 May 2012 / Published: 11 May 2012
PDF Full-text (227 KB)
Abstract
The stability of formulated carotenoid diets during feed processing and under different storage conditions were studied. All carotenoid diets were split into two groups with one group containing BHT (acting as an antioxidant) at 250 ppm and the other without BHT. The [...] Read more.
The stability of formulated carotenoid diets during feed processing and under different storage conditions were studied. All carotenoid diets were split into two groups with one group containing BHT (acting as an antioxidant) at 250 ppm and the other without BHT. The experiment was divided into two parts. First, all diets were evaluated in total carotenoid (TC) loss during feed processing, in dry mixed feeds after being processed and dried. In the final part, the completed dietary carotenoids were stored in an aluminum foil bag, the top of which was sealed with a bag sealer and kept under different storage conditions at 26–28 °C and 4 °C. The stability of the TC was observed during an 8-week trial period. The results showed that the diet pelleting process did not affect the carotenoid content of the diets, and the best storage temperature for the formulated carotenoid diet was at 4 °C. However, an antioxidant was added to assist in energy saving before feed processing. Thus, the addition of BHT at 250 ppm can be done at normal room temperature in order to reduce oxidation that might cause a loss of TC quantities in diets. Full article
(This article belongs to the Special Issue Carotenoids)
Open AccessArticle Optimization of a Microwave-Coupled Enzymatic Digestion Process to Prepare Peanut Peptides
Molecules 2012, 17(5), 5661-5674; doi:10.3390/molecules17055661
Received: 14 March 2012 / Revised: 3 May 2012 / Accepted: 7 May 2012 / Published: 11 May 2012
Cited by 2 | PDF Full-text (496 KB)
Abstract
The best enzyme to prepare peanut peptides, papain, coupled with microwave irradiation was selected from five common proteases according to the results of the yield of peanut peptides [nitrogen solution index (NSI) in trichloroacetic acid (TCA), TCA-NSI] and the degree of hydrolysis [...] Read more.
The best enzyme to prepare peanut peptides, papain, coupled with microwave irradiation was selected from five common proteases according to the results of the yield of peanut peptides [nitrogen solution index (NSI) in trichloroacetic acid (TCA), TCA-NSI] and the degree of hydrolysis (DH). The main factors that influenced the microwave-coupled enzymatic digestion method were optimized by response surface analysis. The optimal conditions obtained were as follows: microwave extraction time, 9.5 min; power, 600 W; substrate concentration, 4%; enzymatic reaction temperature, 50 °C; enzyme quantity, 6,500 U/g; pH, 7.1 (phosphate buffer, 0.05 mol/L). Under these conditions, TCA-NSI was 62.00% and DH was 25.89%, which is higher than that obtained with either protease hydrolysis or microwave hydrolysis alone. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Development of a Method for the Preparation of Ruthenium Indenylidene-Ether Olefin Metathesis Catalysts
Molecules 2012, 17(5), 5675-5689; doi:10.3390/molecules17055675
Received: 28 March 2012 / Revised: 18 April 2012 / Accepted: 23 April 2012 / Published: 11 May 2012
Cited by 9 | PDF Full-text (345 KB)
Abstract
The reactions between several derivatives of 1-(3,5-dimethoxyphenyl)-prop-2-yn-1-ol and different ruthenium starting materials [i.e., RuCl2(PPh3)3 and RuCl2(p-cymene)(L), where L is tricyclohexylphosphine di-t-butylmethylphosphine, dicyclohexylphenylphosphine, triisobutylphosphine, triisopropylphosphine, or tri-n-propylphosphine] are described. Several [...] Read more.
The reactions between several derivatives of 1-(3,5-dimethoxyphenyl)-prop-2-yn-1-ol and different ruthenium starting materials [i.e., RuCl2(PPh3)3 and RuCl2(p-cymene)(L), where L is tricyclohexylphosphine di-t-butylmethylphosphine, dicyclohexylphenylphosphine, triisobutylphosphine, triisopropylphosphine, or tri-n-propylphosphine] are described. Several of these reactions allow for the easy, in-situ and atom-economic preparation of olefin metathesis catalysts. Organic precursor 1-(3,5-dimethoxyphenyl)-1-phenyl-prop-2-yn-1-ol led to the formation of active ruthenium indenylidene-ether complexes, while 1-(3,5-dimethoxyphenyl)-prop-2-yn-1-ol and 1-(3,5-dimethoxyphenyl)-1-methyl-prop-2-yn-1-ol did not. It was also found that a bulky and strong σ-donor phosphine ligand was required to impart good catalytic activity to the new ruthenium complexes. Full article
(This article belongs to the Special Issue Olefin Metathesis and Its Application)
Open AccessArticle QSAR Modeling on Benzo[c]phenanthridine Analogues as Topoisomerase I Inhibitors and Anti-cancer Agents
Molecules 2012, 17(5), 5690-5712; doi:10.3390/molecules17055690
Received: 5 April 2012 / Revised: 25 April 2012 / Accepted: 4 May 2012 / Published: 11 May 2012
Cited by 5 | PDF Full-text (762 KB) | Supplementary Files
Abstract
Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, hologram-QSAR, 2D-QSAR and 3D-QSAR models were developed for BCPs on topoisomerase I inbibitory activity and cytotoxicity against seven tumor cell lines including [...] Read more.
Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, hologram-QSAR, 2D-QSAR and 3D-QSAR models were developed for BCPs on topoisomerase I inbibitory activity and cytotoxicity against seven tumor cell lines including RPMI8402, CPT-K5, P388, CPT45, KB3-1, KBV-1and KBH5.0. The hologram, 2D, and 3D-QSAR models were obtained with the square of correlation coefficient R2 = 0.58 − 0.77, the square of the crossvalidation coefficient q2 = 0.41 − 0.60 as well as the external set’s square of predictive correlation coefficient r2 = 0.51 − 0.80. Moreover, the assessment method based on reliability test with confidence level of 95% was used to validate the predictive power of QSAR models and to prevent over-fitting phenomenon of classical QSAR models. Our QSAR model could be applied to design new analogues of BCPs with higher antitumor and topoisomerase I inhibitory activity. Full article
(This article belongs to the Special Issue QSAR and Its Applications)
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Open AccessArticle Antifungal Activities of New Coumarins
Molecules 2012, 17(5), 5713-5723; doi:10.3390/molecules17055713
Received: 31 March 2012 / Revised: 12 April 2012 / Accepted: 20 April 2012 / Published: 14 May 2012
Cited by 23 | PDF Full-text (1086 KB)
Abstract
Newly synthesized coumarins 4-((5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-methoxy)-2H-chromen-2-one and 4-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)-methoxy)-2H-chromen-2-one were tested against selected types of fungi and showed significant activities. DFT calculations of the synthesized coumarins were performed using molecular structures with optimized geometries. Molecular orbital calculations provide a [...] Read more.
Newly synthesized coumarins 4-((5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-methoxy)-2H-chromen-2-one and 4-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)-methoxy)-2H-chromen-2-one were tested against selected types of fungi and showed significant activities. DFT calculations of the synthesized coumarins were performed using molecular structures with optimized geometries. Molecular orbital calculations provide a detailed description of the orbitals, including spatial characteristics, nodal patterns, and the contributions of individual atoms. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis of a 2,2'-Bipyridyl Functionalized Oligovinylene-Phenylene Using Heck and Horner-Wadsworth-Emmons Reactions and X-ray Crystal Structure of E-(4-(4-Bromostyryl)phenyl)(methyl)sulfane
Molecules 2012, 17(5), 5724-5732; doi:10.3390/molecules17055724
Received: 8 March 2012 / Revised: 3 May 2012 / Accepted: 7 May 2012 / Published: 14 May 2012
Cited by 1 | PDF Full-text (528 KB) | Supplementary Files
Abstract
The synthesis of a new 2,2'-bipyridyl functionalized oligovinylenephenylene (OVP-5) containing a methyl protected thiol using Heck coupling and the Horner-Wadsworth-Emmons reaction and is described. A key step involving a diisopropylcarbodiimide promoted dehydration of a stable b-hydroxyphosphonate intermediate was identified. The [...] Read more.
The synthesis of a new 2,2'-bipyridyl functionalized oligovinylenephenylene (OVP-5) containing a methyl protected thiol using Heck coupling and the Horner-Wadsworth-Emmons reaction and is described. A key step involving a diisopropylcarbodiimide promoted dehydration of a stable b-hydroxyphosphonate intermediate was identified. The structure of precursor E-(4-(4-bromostyryl)phenyl)(methyl)sulfane (1) was determined using X-ray crystallography. Full article
(This article belongs to the Section Organic Synthesis)
Open AccessArticle Anticancer Properties and Phenolic Contents of Sequentially Prepared Extracts from Different Parts of Selected Medicinal Plants Indigenous to Malaysia
Molecules 2012, 17(5), 5745-5756; doi:10.3390/molecules17055745
Received: 6 April 2012 / Revised: 12 May 2012 / Accepted: 14 May 2012 / Published: 14 May 2012
Cited by 12 | PDF Full-text (327 KB)
Abstract
Different parts of four edible medicinal plants (Casearia capitellata, Baccaurea motleyana, Phyllanthus pulcher and Strobilanthus crispus), indigenous to Malaysia, were extracted in different solvents, sequentially. The obtained 28 extracts were evaluated for their in vitro anticancer properties, using the MTS assay, on four human cancer cell lines: colon (HT-29), breast (MCF-7), prostate (DU-145) and lung (H460) cancers. The best anticancer activity was observed for the ethyl acetate (EA) extract of Casearia capitellata leaves on MCF-7 cell lines with IC50 2.0 μg/mL and its methanolic (MeOH) extract showed an outstanding activity against lung cancer cell lines. Dichloromethane (DCM) extract of Phyllanthus pulcher aerial parts showed the highest anticancer activity against DU-145 cell lines, while significant activity was exhibited by DCM extract of Phyllanthus pulcher roots on colon cancer cell lines with IC50 value of 8.1 μg/mL. Total phenolic content (TPC) ranged over 1–40 mg gallic acid equivalents (GAE)/g. For all the samples, highest yields of phenolics were obtained for MeOH extracts. Among all the extracts analyzed, the MeOH extracts of Strobilanthus crispus leaves exhibited the highest TPC than other samples (p < 0.05). This study shows that the nature of phenol determines its anticaner activity and not the number of phenols present. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Protective Effects of Extracts and Flavonoids Isolated from Scutia buxifolia Reissek against Chromosome Damage in Human Lymphocytes Exposed to Hydrogen Peroxide
Molecules 2012, 17(5), 5757-5769; doi:10.3390/molecules17055757
Received: 26 March 2012 / Revised: 25 April 2012 / Accepted: 26 April 2012 / Published: 14 May 2012
Cited by 15 | PDF Full-text (317 KB)
Abstract
Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of crude extract, ethyl acetate fraction and flavonoids (quercetin, quercitrin, isoquercitrin and rutin) isolated from the [...] Read more.
Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of crude extract, ethyl acetate fraction and flavonoids (quercetin, quercitrin, isoquercitrin and rutin) isolated from the leaves from Scutia buxifolia against chromosome damage induced by H2O2 in human lymphocytes by analyzing cellular growth rate, cell viability, mitotic index and chromosomal instability. We found a differential response among the compounds tested, with the ethyl acetate fraction being more effective than the crude extract, a difference perhaps related to the presence of the antioxidants identified and quantified by HPLC/DAD. In general, quercetin, isoquercitrin and rutin recovered the mitotic index and chromosomal instability more than quercitrin after treatment with hydrogen peroxide. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Synthesis of Novel E-2-Chlorovinyltellurium Compounds Based on the Stereospecific Anti-addition of Tellurium Tetrachloride to Acetylene
Molecules 2012, 17(5), 5770-5779; doi:10.3390/molecules17055770
Received: 5 April 2012 / Revised: 6 May 2012 / Accepted: 8 May 2012 / Published: 15 May 2012
Cited by 18 | PDF Full-text (181 KB)
Abstract
The reaction of tellurium tetrachloride with acetylene proceeds in a stereospecific anti-addition manner to afford the novel products E-2-chlorovinyltellurium trichloride and E,E-bis(2-chlorovinyl)tellurium dichloride. Reaction conditions for the selective preparation of each of these products were found. The [...] Read more.
The reaction of tellurium tetrachloride with acetylene proceeds in a stereospecific anti-addition manner to afford the novel products E-2-chlorovinyltellurium trichloride and E,E-bis(2-chlorovinyl)tellurium dichloride. Reaction conditions for the selective preparation of each of these products were found. The latter was obtained in 90% yield in CHCl3 under a pressure of acetylene of 10–15 atm, whereas the former product was formed in up to 72% yield in CCl4 under a pressure of acetylene of 1–3 atm. Synthesis of the previously unknown E,E-bis(2-chlorovinyl) telluride, E,E-bis(2-chlorovinyl) ditelluride, E-2-chlorovinyl 1,2,2-trichloroethyl telluride and E,E-bis(2-chlorovinyl)-tellurium dibromide is described. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Luffa echinata Roxb. Induces Human Colon Cancer Cell (HT-29) Death by Triggering the Mitochondrial Apoptosis Pathway
Molecules 2012, 17(5), 5780-5794; doi:10.3390/molecules17055780
Received: 19 March 2012 / Revised: 9 May 2012 / Accepted: 11 May 2012 / Published: 16 May 2012
Cited by 14 | PDF Full-text (582 KB)
Abstract
The antiproliferative properties and cell death mechanism induced by the extract of the fruits of Luffa echinata Roxb. (LER) were investigated. The methanolic extract of LER inhibited the proliferation of human colon cancer cells (HT-29) in both dose-dependent and time-dependent manners and [...] Read more.
The antiproliferative properties and cell death mechanism induced by the extract of the fruits of Luffa echinata Roxb. (LER) were investigated. The methanolic extract of LER inhibited the proliferation of human colon cancer cells (HT-29) in both dose-dependent and time-dependent manners and caused a significant increase in the population of apoptotic cells. In addition, obvious shrinkage and destruction of the monolayer were observed in LER-treated cells, but not in untreated cells. Analysis of the cell cycle after treatment of HT-29 cells with various concentrations indicated that LER extracts inhibited the cellular proliferation of HT-29 cells via G2/M phase arrest of the cell cycle. The Reactive oxygen species (ROS) level determination revealed that LER extracts induced apoptotic cell death via ROS generation. In addition, LER treatment led to a rapid drop in mitochondrial membrane potential (MMP) as a decrease in fluorescence. The transcripts of several apoptosis-related genes were investigated by RT-PCR analysis. The caspase-3 transcripts of HT-29 cells significantly accumulated and the level of Bcl-XL mRNA was decreased after treatment with LER extract. Furthermore, the ratio of mitochondria-dependent apoptosis genes (Bax and Bcl-2) was sharply increased from 1.6 to 54.1. These experiments suggest that LER has anticancer properties via inducing the apoptosis in colon cancer cells, which provided the impetus for further studies on the therapeutic potential of LER against human colon carcinoma. Full article
Open AccessArticle A New Facile Synthesis of D4-Pterosin B and D4-Bromopterosin, Deuterated Analogues of Ptaquiloside
Molecules 2012, 17(5), 5795-5802; doi:10.3390/molecules17055795
Received: 26 April 2012 / Revised: 9 May 2012 / Accepted: 14 May 2012 / Published: 16 May 2012
Cited by 5 | PDF Full-text (218 KB)
Abstract
Ptaquiloside (Pta) is a potent carcinogen present in bracken fern and in soil matrices, that can potentially leach to the aquatic environment. More recently its presence in the milk of different farm animals has been reported. Pterosin B (Ptb) and bromopterosin (BrPt) [...] Read more.
Ptaquiloside (Pta) is a potent carcinogen present in bracken fern and in soil matrices, that can potentially leach to the aquatic environment. More recently its presence in the milk of different farm animals has been reported. Pterosin B (Ptb) and bromopterosin (BrPt) represent the most convenient analogues in the detection of ptaquiloside by mass spectrometry. Pterosin sesquiterpenes are also involved in many patented biomedical protocols. In this work we introduce a new and convenient approach to the synthesis in three steps and more than 80% yield of d4-pterosin B (d4-Ptb) and d4-bromopterosin (d4-BrPt), useful as internal standards in the quantification of ptaquiloside. Full article
(This article belongs to the Special Issue Challenges in Synthetic Chemistry)
Open AccessArticle A Study of Proline Metabolism in Canola (Brassica napus L.) Seedlings under Salt Stress
Molecules 2012, 17(5), 5803-5815; doi:10.3390/molecules17055803
Received: 7 March 2012 / Revised: 25 April 2012 / Accepted: 26 April 2012 / Published: 16 May 2012
Cited by 10 | PDF Full-text (279 KB)
Abstract
Expression analysis of crop plants has improved our knowledge about the veiled underlying mechanisms for salt tolerance. In order to observe the time course effects of salinity stress on gene expression for enzymes regulating proline metabolism, we comparatively analyzed the expression of [...] Read more.
Expression analysis of crop plants has improved our knowledge about the veiled underlying mechanisms for salt tolerance. In order to observe the time course effects of salinity stress on gene expression for enzymes regulating proline metabolism, we comparatively analyzed the expression of specific genes for proline metabolism in root and shoot tissues of salt-tolerant (cv. Dunkled) and salt-sensitive (cv. Cyclone) canola (Brassica napus L.) cultivars through reverse-transcriptase polymerase chain reaction (RT-PCR); following the NaCl treatment for various durations. Both lines showed an increase in ∆1-pyrroline-5-carboxylate synthase1 (P5CS1) gene expression after induction of salt stress with enhanced expression in the root tissue of the tolerant line, while maximum expression was noted in the shoot tissues of the sensitive line. We observed a much reduced proline dehydrogenase (PDH) expression in both the root and shoot tissues of both canola lines, with more marked reduction of PDH expression in the shoot tissues than that in the root ones. To confirm the increase in P5CS1 gene expression, total proline content was also measured in the root and shoot tissues of both the canola lines. The root tissues of canola sensitive line showed a gradually increasing proline concentration pattern with regular increase in salinity treatment, while an increase in proline concentration in the tolerant line was noted at 24 h post salinity treatment after a sudden decrease at 6 h and 12 h of salt treatment. A gradually increasing concentration of free proline content was found in shoot tissues of the tolerant canola line though a remarkable increase in proline concentration was noted in the sensitive canola line at 24 h post salinity treatment, indicating the initiation of proline biosynthesis process in that tissue of sensitive canola. Full article
Open AccessArticle Chemical Investigation of Saponins in Different Parts of Panax notoginseng by Pressurized Liquid Extraction and Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry
Molecules 2012, 17(5), 5836-5853; doi:10.3390/molecules17055836
Received: 12 April 2012 / Revised: 3 May 2012 / Accepted: 11 May 2012 / Published: 16 May 2012
Cited by 18 | PDF Full-text (527 KB)
Abstract
A pressurized liquid extraction (PLE) and high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for the qualitative determination of saponins in different parts of P. notoginseng, including rhizome, root, fibre root, seed, stem, leaf and flower. The [...] Read more.
A pressurized liquid extraction (PLE) and high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for the qualitative determination of saponins in different parts of P. notoginseng, including rhizome, root, fibre root, seed, stem, leaf and flower. The samples were extracted using PLE. The analysis was achieved on a Zorbax SB-C18 column with gradient elution of acetonitrile and 8 mM aqueous ammonium acetate as mobile phase. The mass spectrometer was operated in the negative ion mode using the electrospray ionization, and a collision induced dissociation (CID) experiment was also carried out to aid the identification of compounds. Forty one saponins were identified in different parts of P. notoginseng according to the fragmentation patterns and literature reports, among them, 21 saponins were confirmed by comparing the retention time and ESI-MS data with those of standard compounds. The results showed that the chemical characteristics were obviously diverse in different parts of P. notoginseng, which is helpful for pharmacological evaluation and quality control of P. notoginseng. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Effects of Citrus aurantium (Bitter Orange) Fruit Extracts and p-Synephrine on Metabolic Fluxes in the Rat Liver
Molecules 2012, 17(5), 5854-5869; doi:10.3390/molecules17055854
Received: 21 March 2012 / Revised: 7 May 2012 / Accepted: 12 May 2012 / Published: 16 May 2012
Cited by 10 | PDF Full-text (363 KB)
Abstract
The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite supressants. An important fruit component is p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss and adrenergic actions are always related to metabolic [...] Read more.
The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite supressants. An important fruit component is p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss and adrenergic actions are always related to metabolic changes and this work was designed to investigate a possible action of the C. aurantium extract on liver metabolism. The isolated perfused rat liver was used to measure catabolic and anabolic pathways, including oxygen uptake and perfusion pressure. The C. aurantium extract and p-synephrine increased glycogenolysis, glycolysis, oxygen uptake and perfusion pressure. These changes were partly sensitive to a- and b-adrenergic antagonists. p-Synephrine (200 mM) produced an increase in glucose output that was only 15% smaller than the increment caused by the extract containing 196 mM p-synephrine. At low concentrations the C. aurantium extract tended to increase gluconeogenesis, but at high concentrations it was inhibitory, opposite to what happened with p-synephrine. The action of the C. aurantium extract on liver metabolism is similar to the well known actions of adrenergic agents and can be partly attributed to its content in p-synephrine. Many of these actions are catabolic and compatible with the weight-loss effects usually attributed to C. aurantium. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Design, Synthesis and Antiproliferative Activity of Novel 2-Substituted-4-amino-6-halogenquinolines
Molecules 2012, 17(5), 5870-5881; doi:10.3390/molecules17055870
Received: 28 April 2012 / Revised: 10 May 2012 / Accepted: 11 May 2012 / Published: 16 May 2012
Cited by 6 | PDF Full-text (303 KB)
Abstract
Two series of novel 2-substituted-4-amino-6-halogenquinolines 8al and 13ah were designed, synthesized and evaluated for their antiproliferative activity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. The pharmacological results indicated that most compounds with 2-arylvinyl [...] Read more.
Two series of novel 2-substituted-4-amino-6-halogenquinolines 8al and 13ah were designed, synthesized and evaluated for their antiproliferative activity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. The pharmacological results indicated that most compounds with 2-arylvinyl substituents exhibited good to excellent antiproliferative activity. Among them, compound 8e was a considered promising lead for further structural modifications with IC50 values of 0.03 μM, 0.55 μM, 0.33 μM and 1.24 μM, which was 2.5- to 186-fold more active than gefitinib and compound 1. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of 1,2,3-Triazole Derivatives and in Vitro Antifungal Evaluation on Candida Strains
Molecules 2012, 17(5), 5882-5892; doi:10.3390/molecules17055882
Received: 12 April 2012 / Revised: 3 May 2012 / Accepted: 5 May 2012 / Published: 16 May 2012
Cited by 14 | PDF Full-text (230 KB)
Abstract
1,2,3-Triazoles have been extensively studied as compounds possessing important biological activities. In this work, we describe the synthesis of ten 2-(1-aryl-1H-1,2,3-triazol-4-yl)propan-2-ols via copper catalyzed azide alkyne cycloaddition (CuAAc or click chemistry). Next the in vitro antifungal activity of these [...] Read more.
1,2,3-Triazoles have been extensively studied as compounds possessing important biological activities. In this work, we describe the synthesis of ten 2-(1-aryl-1H-1,2,3-triazol-4-yl)propan-2-ols via copper catalyzed azide alkyne cycloaddition (CuAAc or click chemistry). Next the in vitro antifungal activity of these ten compounds was evaluated using the microdilution broth method against 42 isolates of four different Candida species. Among all tested compounds, the halogen substituted triazole 2-[1-(4-chlorophenyl)-1H-(1,2,3)triazol-4-yl]propan-2-ol, revealed the best antifungal profile, showing that further modifications could be done in the structure to obtain a better drug candidate in the future. Full article
Open AccessArticle Tropical Plant Extracts as Potential Antihyperglycemic Agents
Molecules 2012, 17(5), 5915-5923; doi:10.3390/molecules17055915
Received: 7 April 2012 / Revised: 28 April 2012 / Accepted: 30 April 2012 / Published: 18 May 2012
Cited by 8 | PDF Full-text (605 KB)
Abstract
Preliminary investigations on 14 plant extracts (obtained by ethanolic and aqueous extraction) identified those having high antioxidant and a significant total phenolic content. Antihyperglycemic, a-amylase and a-glucosidase inhibition activities were also observed. A correlation between the antihyperglycemic activity, total phenolic content and [...] Read more.
Preliminary investigations on 14 plant extracts (obtained by ethanolic and aqueous extraction) identified those having high antioxidant and a significant total phenolic content. Antihyperglycemic, a-amylase and a-glucosidase inhibition activities were also observed. A correlation between the antihyperglycemic activity, total phenolic content and antioxidant (DPPH scavenging) activity was established. To further substantiate these findings, the possibility of tannins binding non-specifically to enzymes and thus contributing to the antihyperglycemic activity was also investigated. Our study clearly indicated that the antihyperglycemic activity observed in the plant extracts was indeed not due to non-specific tannin absorption. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Scope and Limitations of a Novel Synthesis of 3-Arylazonicotinates
Molecules 2012, 17(5), 5924-5934; doi:10.3390/molecules17055924
Received: 27 January 2012 / Revised: 13 May 2012 / Accepted: 15 May 2012 / Published: 18 May 2012
Cited by 3 | PDF Full-text (214 KB) | Supplementary Files
Abstract The reaction of 3-oxo-3-phenyl-2-phenylhydrazonal with functionally substituted and heteroaromatic substituted acetonitrile to yield arylazonicotinic acid derivatives and 5-arylsubstituted pyridines was established. In some cases the produced nicotinates could not be isolated as they underwent thermally induced 6π-electrocyclization yielding polynuclear pyridine derivatives. Full article
(This article belongs to the Special Issue Heterocycles)
Open AccessArticle The Vasorelaxant Mechanisms of a Rho Kinase Inhibitor DL0805 in Rat Thoracic Aorta
Molecules 2012, 17(5), 5935-5944; doi:10.3390/molecules17055935
Received: 26 March 2012 / Revised: 11 May 2012 / Accepted: 11 May 2012 / Published: 18 May 2012
Cited by 6 | PDF Full-text (402 KB)
Abstract
Rho-kinase has been suggested as a potential therapeutic target in the treatment of cardiovascular diseases. The Rho-kinase signaling pathway is substantially involved in vascular contraction. The aim of the present study was to evaluate the vasorelaxant effects of Rho kinase inhibitor DL0805 [...] Read more.
Rho-kinase has been suggested as a potential therapeutic target in the treatment of cardiovascular diseases. The Rho-kinase signaling pathway is substantially involved in vascular contraction. The aim of the present study was to evaluate the vasorelaxant effects of Rho kinase inhibitor DL0805 in isolated rat aortic rings and to investigate its possible mechanism(s). It was found that DL0805 exerted vasorelaxation in a dose-dependent manner in NE or KCl-induced sustained contraction and partial loss of the vasorelaxation under endothelium-denuded rings. The DL0805-induced vasorelaxation was significantly reduced by the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester, the guanylate cyclase inhibitor methylene blue and the cyclooxygenase inhibitor indomethacin. The voltage-dependent K+ channel blocker 4-aminopyridine remarkably attenuated DL0805-induced relaxations. However, the ATP-sensitive K+ channel blocker glibenclamide and Ca2+-activated K+ channel blocker tetraethylammonium did not affect the DL0805-induced relaxation. In the endothelium-denuded rings, DL0805 also reduced NE-induced transient contraction and inhibited contraction induced by increasing external calcium. These findings suggested that DL0805 is a novel vasorelaxant compound associated with inhibition of Rho/ROCK signaling pathway. The NO-cGMP pathway may be involved in the relaxation of DL0805 in endothelium-intact aorta. The vasorelaxant effect of DL0805 is partially mediated by the opening of the voltage-dependent K+ channels. Full article
Open AccessCommunication Inhibitory Effect and Mechanism on Antiproliferation of Isoatriplicolide Tiglate (PCAC) from Paulownia Coreana
Molecules 2012, 17(5), 5945-5951; doi:10.3390/molecules17055945
Received: 28 April 2012 / Revised: 11 May 2012 / Accepted: 14 May 2012 / Published: 18 May 2012
Cited by 3 | PDF Full-text (599 KB) | Correction
Abstract
Paulownia coreana has traditionally been used as the medicine and health food in the treatment of cancer and infectious diseases. In the present study, a new antiproliferation agent, isoatriplicolide tiglate (PCAC) was isolated from the chloroform soluble fraction of the leaves of Paulownia coreana. The antiproliferation activities of PCAC plant extract was examined in breast and cervical cancer cell lines in a time-and dose-dependent manners. Our in vitro experiments showed that PCAC suppresses the cell growth and proliferation of cancer cells at a relatively low concentration ( < 10 µg/mL) and induces apoptosis at a high concentration ( > 50 µg/mL). Western blot analysis showed that concentration higher than 50 µg/mL induces a time-dependent increase in the percentage of apoptotic cells. In this case, PCAC uses both extrinsic and intrinsic pathways for the apoptosis. PCAC treatment decreased the expression of pro-caspase 8, 9, and 3, the main regulators of apoptotic cell death, in MDA-MB-231 cells, accompanied by the activation of caspase 8, 9, and 3. More importantly, PCAC inhibited the in vitro proliferation of six other human breast and cervical cancer cell lines. In conclusion, our data strongly suggest that PCAC acts as an antiproliferation agents particularly against breast and cervical cancers by inducing cell cycle arrest in the S/G2 phase and caspase dependent apoptosis at relatively low ( < 10 μg/mL) and high ( > 50 µg/mL) concentrations, respectively. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Antibacterial Evaluation of Some Schiff Bases Derived from 2-Acetylpyridine and Their Metal Complexes
Molecules 2012, 17(5), 5952-5971; doi:10.3390/molecules17055952
Received: 27 March 2012 / Revised: 13 May 2012 / Accepted: 15 May 2012 / Published: 18 May 2012
Cited by 14 | PDF Full-text (436 KB)
Abstract
A series of Schiff bases derived from 2-acetylpyridne and their metal complexes were characterized by elemental analysis, NMR, FT-IR and UV-Vis spectral studies. The complexes were screened for anti-bacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumanni (AC), Klebsiella pneumonie (KB) and [...] Read more.
A series of Schiff bases derived from 2-acetylpyridne and their metal complexes were characterized by elemental analysis, NMR, FT-IR and UV-Vis spectral studies. The complexes were screened for anti-bacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumanni (AC), Klebsiella pneumonie (KB) and Pseudomonas aeruginosa (PA) using the disc diffusion and micro broth dilution assays. Based on the overall results, the complexes showed the highest activities against MRSA while a weak antibacterial activity was observed against A. baumanii and P. aeruginosa. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Preparation of Curcumin-Loaded Liposomes and Evaluation of Their Skin Permeation and Pharmacodynamics
Molecules 2012, 17(5), 5972-5987; doi:10.3390/molecules17055972
Received: 9 April 2012 / Revised: 8 May 2012 / Accepted: 9 May 2012 / Published: 18 May 2012
Cited by 48 | PDF Full-text (708 KB)
Abstract
This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation [...] Read more.
This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation of different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C-HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different lipsomes were investigated as follows: photon correlation spectroscopy revealed that the average particle sizes of the three types of curcumin-loaded liposomes were 82.37 ± 2.19 nm (C-SPC-L), 83.13 ± 4.89 nm (C-EPC-L), and 92.42 ± 4.56 nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be 82.32 ± 3.91%, 81.59 ± 2.38%, and 80.77 ± 4.12%, respectively. An in vitro skin penetration study indicated that C-SPC-L most significantly promoted drug permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution. Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen for further pharmacodynamic evaluation. A significant effect on antimelanoma activity was observed with C-SPC-L, as compared to treatment with curcumin solution in vivo. These results suggest that C-SPC-L would be a promising transdermal carrier for curcumin in cancer treatment. Full article
Open AccessArticle A Sandwich HIV p24 Amperometric Immunosensor Based on a Direct Gold Electroplating-Modified Electrode
Molecules 2012, 17(5), 5988-6000; doi:10.3390/molecules17055988
Received: 8 March 2012 / Revised: 25 April 2012 / Accepted: 9 May 2012 / Published: 18 May 2012
Cited by 22 | PDF Full-text (590 KB)
Abstract
Acquired immune deficiency syndrome (AIDS) is a severe communicable immune deficiency disease caused by the human immune deficiency virus (HIV). The analysis laboratory diagnosis of HIV infection is a crucial aspect of controlling AIDS. The p24 antigen, the HIV-1 capsid protein, is [...] Read more.
Acquired immune deficiency syndrome (AIDS) is a severe communicable immune deficiency disease caused by the human immune deficiency virus (HIV). The analysis laboratory diagnosis of HIV infection is a crucial aspect of controlling AIDS. The p24 antigen, the HIV-1 capsid protein, is of considerable diagnostic interest because it is detectable several days earlier than host-generated HIV antibodies following HIV exposure. We present herein a new sandwich HIV p24 immunosensor based on directly electroplating an electrode surface with gold nanoparticles using chronoamperometry, which greatly increased the conductivity and reversibility of the electrode. Under optimum conditions, the electrochemical signal showed a linear relationship with the concentration of p24, ranging from 0.01 ng/mL to 100 ng/mL (R > 0.99), and the detection limit was 0.008 ng/mL. Compared with ELISA, this method increased the sensitivity by more than two orders of magnitude (the sensitivity of ELISA for p24 is about 1 ng/mL). This immunosensor may be broadly applied to clinical samples, being distinguished by its ease of use, mild reaction conditions, guaranteed reproducibility, and good anti-interference ability. Full article
Open AccessArticle Metathesis Transformations of Natural Products: Cross-Metathesis of Natural Rubber and Mandarin Oil by Ru-Alkylidene Catalysts
Molecules 2012, 17(5), 6001-6010; doi:10.3390/molecules17056001
Received: 16 March 2012 / Revised: 30 April 2012 / Accepted: 3 May 2012 / Published: 18 May 2012
Cited by 9 | PDF Full-text (245 KB)
Abstract
This study reports on the degradation of natural rubber (NR) via cross-metathesis with mandarin oil and d-limonene, an abundant compound in essential oils; that were used as chain transfer agents (CTAs) and green solvents. Reactions were performed in the presence of [...] Read more.
This study reports on the degradation of natural rubber (NR) via cross-metathesis with mandarin oil and d-limonene, an abundant compound in essential oils; that were used as chain transfer agents (CTAs) and green solvents. Reactions were performed in the presence of the ruthenium-alkylidene catalysts (PCy3)2(Cl)2Ru=CHPh (I) and (1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) (PCy3)Cl2Ru=CHPh (II), respectively. Catalyst II bears an N-heterocyclic carbene ligand (NHC) bounded to the ruthenium atom, which has a strong basic character; therefore it is more active toward trisubstituted olefins in comparison with catalyst I. In both cases, isolated monoterpene-terminated isoprene oligomers were obtained as products of the cross-metathesis degradation of NR. In the presence of catalyst II molecular weight values around Mn × 102 and yields of 80% were obtained; whereas with catalyst I, the molecular weights of products were about Mn × 104 with yields ranging 70 to 74%. The composition and yield of NR degradation products were determined by GC/MS (EI) analysis and it was found that the oligomers obtained have primarily one vinyl group and one terpene-monocyclic group at the chain end, with isoprene units Am = 2, 3 y 4. Full article
(This article belongs to the Special Issue Olefin Metathesis and Its Application)
Open AccessArticle Green and Highly Efficient Synthesis of 2-Arylbenzothiazoles Using Glycerol without Catalyst at Ambient Temperature
Molecules 2012, 17(5), 6011-6019; doi:10.3390/molecules17056011
Received: 27 March 2012 / Revised: 9 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012
Cited by 16 | PDF Full-text (175 KB)
Abstract A one-pot and clean synthesis of 2-arylbenzothiazoles via the ambient temperature reaction of 2-aminothiophenols and aromatic aldehydes without catalyst in glycerol as a green solvent has been reported. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Chemical Composition of Artemisia annua L. Leaves and Antioxidant Potential of Extracts as a Function of Extraction Solvents
Molecules 2012, 17(5), 6020-6032; doi:10.3390/molecules17056020
Received: 12 April 2012 / Revised: 9 May 2012 / Accepted: 11 May 2012 / Published: 21 May 2012
Cited by 13 | PDF Full-text (237 KB)
Abstract
This study was conducted to investigate the chemical and nutritional composition of Artemisia annua leaves in addition to determination of antioxidant potential of their extracts prepared in different solvents. Chemical composition was determined by quantifying fat, protein, carbohydrate, fiber, tocopherol, phytate, and [...] Read more.
This study was conducted to investigate the chemical and nutritional composition of Artemisia annua leaves in addition to determination of antioxidant potential of their extracts prepared in different solvents. Chemical composition was determined by quantifying fat, protein, carbohydrate, fiber, tocopherol, phytate, and tannin contents. Extraction of A. annua leaves, for antioxidant potential evaluation, was carried out using five solvents of different polarities, i.e., hexane, chloroform, ethyl acetate, methanol and water. Antioxidant potential was evaluated by estimating total phenolic (TPC), flavonoid (TFC) contents, ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), DPPH radical scavenging activity and lipid peroxidation. Efficiency of different solvents was compared for the yield of antioxidant extracts from leaf samples and a clear variation was observed. The highest TPC, TFC, TEAC, DPPH radical scavenging and lowest lipid peroxidation were observed in MeOH extracts, whereas aqueous extract exhibited high ferric reducing antioxidant power; suggesting MeOH to be the most favorable extractant. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Protective Effect of T. violacea Rhizome Extract Against Hypercholesterolemia-Induced Oxidative Stress in Wistar Rats
Molecules 2012, 17(5), 6033-6045; doi:10.3390/molecules17056033
Received: 29 March 2012 / Revised: 27 April 2012 / Accepted: 28 April 2012 / Published: 21 May 2012
Cited by 8 | PDF Full-text (368 KB)
Abstract
The present study examines the effect of methanolic extract of T. violacea rhizomes on high cholesterol (2%) diet fed rats (HCD). At the end of 4 weeks, serum total protein, albumin, reduced glutathione (GSH), and markers of oxidative stress viz., catalase (CAT), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS—a marker of lipid peroxidation), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in the serum, aorta, liver and heart of HCD and normal rats were assessed and compared. A significant (p < 0.05) elevation in TBARS, and a reduction (p < 0.05) in serum total protein, albumin, GSH and antioxidant enzyme activities was observed in tissues of HCD fed rats compared with the normal group. Co-administration of crude extracts of T. violacea rhizomes protected the liver, heart, serum and aorta against HCD-induced lipid peroxidation in a dose dependant manner. The activities of the extract (500 mg/kg) compared favorably with gemfibrozil. The extracts also protected against HCD-induced reduction in serum total protein, GSH and restored the activities of antioxidant tissues (liver, heart and aorta) enzymes to near normal values. This result suggested that consumption of T. violacea rhizome may help to protect against hypercholesterolemia- induced oxidative stress diseases in the heart and liver. Full article
Open AccessArticle Effect of Soluble Sulfide on the Activity of Luminescent Bacteria
Molecules 2012, 17(5), 6046-6055; doi:10.3390/molecules17056046
Received: 23 February 2012 / Revised: 11 May 2012 / Accepted: 14 May 2012 / Published: 21 May 2012
Cited by 4 | PDF Full-text (476 KB)
Abstract
Sulfide is an important water pollutant widely found in industrial waste water that has attracted much attention. S2−, as a weak acidic anion, is easy hydrolyzed to HS and H2S in aqueous solution. In this study, biological [...] Read more.
Sulfide is an important water pollutant widely found in industrial waste water that has attracted much attention. S2−, as a weak acidic anion, is easy hydrolyzed to HS and H2S in aqueous solution. In this study, biological tests were performed to establish the toxicity of sulfide solutions on luminescent bacteria. Considering the sulfide solution was contained three substances—S2−, HS and H2S—the toxicity test was performed at different pH values to investigate which form of sulfide increased light emission and which reduced light emission. It was shown that the EC50 values were close at pH 7.4, 8.0 and 9.0 which were higher than pH 5 and 10. The light emission and sulfide concentrations displayed an inverse exponential dose-response relationship within a certain concentration range at pH 5, 6.5 and 10. The same phenomenon occurred for the high concentration of sulfide at pH 7.4, 8 and 9, in which the concentration of sulfide was HS >> H2S > S2−. An opposite hormesis-effect appeared at the low concentrations of sulfide. Full article
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Open AccessArticle Physicochemical Characterization and Cytotoxic Activity Evaluation of Hydroxymethylferrocene:β-Cyclodextrin Inclusion Complex
Molecules 2012, 17(5), 6056-6070; doi:10.3390/molecules17056056
Received: 24 April 2012 / Revised: 14 May 2012 / Accepted: 15 May 2012 / Published: 21 May 2012
Cited by 8 | PDF Full-text (662 KB)
Abstract
An inclusion complex of hydroxymethylferrocene (FeMeOH) with β-cyclodextrin (β-CD) was prepared in the solid state by different techniques such as physical mixture, coprecipitation, kneading and freeze-drying. The formation of the inclusion complex was confirmed by X-ray Powder Diffractometry and Fourier Transform-Infrared spectroscopy. [...] Read more.
An inclusion complex of hydroxymethylferrocene (FeMeOH) with β-cyclodextrin (β-CD) was prepared in the solid state by different techniques such as physical mixture, coprecipitation, kneading and freeze-drying. The formation of the inclusion complex was confirmed by X-ray Powder Diffractometry and Fourier Transform-Infrared spectroscopy. In aqueous solution, the 1:1 stoichiometry was established by a Job plot. The inclusion complex formation was also investigated by NMR and the stability constant (Kb) of the complex was determined to be 478 M−1, which is in agreement with that obtained with UV-Vis tritation (Kb = 541.3 M−1). The phase solubility study showed a diagram classified as BS type and that the solubility of FeMeOH was slightly increased in the presence of β-CD. Furthermore, utilizing phase solubility diagram data, the Kb was estimated to be equal to 528.0 M−1. The cytotoxic activity of FeMeOH and its complexation product with β-CD was determined using the MTT-assay on MDA-MB-231 cell line, showing that the inclusion complex has a higher capability of inhibiting cell growth compared to that of pure FeMeOH. Full article
Open AccessArticle Antioxidant, Antimicrobial and Tyrosinase Inhibitory Activities of Xanthones Isolated from Artocarpus obtusus F.M. Jarrett
Molecules 2012, 17(5), 6071-6082; doi:10.3390/molecules17056071
Received: 5 March 2012 / Revised: 17 April 2012 / Accepted: 20 April 2012 / Published: 21 May 2012
Cited by 18 | PDF Full-text (250 KB)
Abstract
One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone [...] Read more.
One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Synthesis and Evaluation of New β-Carboline-3-(4-benzylidene)-4H-oxazol-5-one Derivatives as Antitumor Agents
Molecules 2012, 17(5), 6100-6113; doi:10.3390/molecules17056100
Received: 5 April 2012 / Revised: 5 May 2012 / Accepted: 7 May 2012 / Published: 21 May 2012
Cited by 10 | PDF Full-text (273 KB) | Supplementary Files
Abstract
In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β-carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4-methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11) was [...] Read more.
In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β-carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4-methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC50 values of 0.48, 1.50 and 1.07 µM, respectively. An in silico study of the ADME properties of the novel synthesized β-carboline derivatives was also performed. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Preussianone, a New Flavanone-Chromone Biflavonoid from Garcinia preussii Engl.
Molecules 2012, 17(5), 6114-6125; doi:10.3390/molecules17056114
Received: 20 March 2012 / Revised: 26 April 2012 / Accepted: 14 May 2012 / Published: 21 May 2012
Cited by 14 | PDF Full-text (273 KB)
Abstract
A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against [...] Read more.
A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against several bacterial strains were evaluated. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle A QSAR Study of Environmental Estrogens Based on a Novel Variable Selection Method
Molecules 2012, 17(5), 6126-6145; doi:10.3390/molecules17056126
Received: 10 March 2012 / Revised: 19 April 2012 / Accepted: 26 April 2012 / Published: 21 May 2012
Cited by 5 | PDF Full-text (718 KB) | Supplementary Files
Abstract
A large number of descriptors were employed to characterize the molecular structure of 53 natural, synthetic, and environmental chemicals which are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones and may thus pose a serious threat to the health [...] Read more.
A large number of descriptors were employed to characterize the molecular structure of 53 natural, synthetic, and environmental chemicals which are suspected of disrupting endocrine functions by mimicking or antagonizing natural hormones and may thus pose a serious threat to the health of humans and wildlife. In this work, a robust quantitative structure-activity relationship (QSAR) model with a novel variable selection method has been proposed for the effective estrogens. The variable selection method is based on variable interaction (VSMVI) with leave-multiple-out cross validation (LMOCV) to select the best subset. During variable selection, model construction and assessment, the Organization for Economic Co-operation and Development (OECD) principles for regulation of QSAR acceptability were fully considered, such as using an unambiguous multiple-linear regression (MLR) algorithm to build the model, using several validation methods to assessment the performance of the model, giving the define of applicability domain and analyzing the outliers with the results of molecular docking. The performance of the QSAR model indicates that the VSMVI is an effective, feasible and practical tool for rapid screening of the best subset from large molecular descriptors. Full article
(This article belongs to the Special Issue QSAR and Its Applications)
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Open AccessArticle Ipomoea aquatica Extract Shows Protective Action Against Thioacetamide-Induced Hepatotoxicity
Molecules 2012, 17(5), 6146-6155; doi:10.3390/molecules17056146
Received: 1 April 2012 / Revised: 20 April 2012 / Accepted: 23 April 2012 / Published: 22 May 2012
Cited by 10 | PDF Full-text (513 KB)
Abstract
In the Indian system of traditional medicine (Ayurveda) it is recommended to consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the protective effects of ethanol extract of I. aquatica against liver damage were evaluated in thioacetamide (TAA)-induced chronic hepatotoxicity in rats. There was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD) rats were orally fed with I. aquatica (250 and 500 mg/kg) for two months along with administration of TAA (i.p injection 200 mg/kg three times a week for two months). The results showed that the treatment of I. aquatica significantly lowered the TAA-induced serum levels of hepatic enzyme markers (ALP, ALT, AST, protein, albumin, bilirubin and prothrombin time). The hepatic content of activities and expressions SOD and CAT that were reduced by TAA were brought back to control levels by the plant extract supplement. Meanwhile, the rise in MDA level in the TAA receiving groups also were significantly reduced by I. aquatica treatment. Histopathology of hepatic tissues by H&E and Masson trichrome stains displayed that I. aquatica has reduced the incidence of liver lesions, including hepatic cells cloudy swelling, infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by TAA in rats. Therefore, the results of this study show that the protective effect of I. aquatica in TAA-induced liver damage might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects. Moreover, it confirms a scientific basis for the traditional use of I. aquatica for the treatment of liver disorders. Full article
(This article belongs to the Section Natural Products)
Open AccessArticle Chemical Constituents of the Ethyl Acetate Extract of Belamcanda chinensis (L.) DC Roots and Their Antitumor Activities
Molecules 2012, 17(5), 6156-6169; doi:10.3390/molecules17056156
Received: 19 April 2012 / Revised: 8 May 2012 / Accepted: 14 May 2012 / Published: 24 May 2012
Cited by 21 | PDF Full-text (539 KB)
Abstract
An activity-directed fractionation and purification process was used to isolate antitumor compounds from the roots of Belamcanda chinensis (L.) DC. The ethyl acetate extract showed greater antitumor activities than the other extracts, consequently leading to the isolation of 18 compounds identified as [...] Read more.
An activity-directed fractionation and purification process was used to isolate antitumor compounds from the roots of Belamcanda chinensis (L.) DC. The ethyl acetate extract showed greater antitumor activities than the other extracts, consequently leading to the isolation of 18 compounds identified as b-sitosterol (1), dausterol (2), quercetin (3), kampferol (4), shikimic acid (5), gallic acid (6), ursolic acid (7), betulin (8), betulonic acid (9), betulone (10), tectoridin (11), irisflorentin (12), 4′,5,6-trihydroxy-7-methoxyisoflavone (13), tectorigenin (14), irilins A (15), iridin (16), irigenin (17), and iristectongenin A (18). Compounds 310, 13, and 15 were isolated from B. chinensis for the first time. Compounds 4 and 710 showed potent cytotoxic activities against PC3, MGC-803, Bcap-37, and MCF-7 cell lines. The mechanism of the antitumor action of compound 7 was preliminarily investigated through acridine orange/ethidium bromide (AO/EB) staining, Hoechst 33258 staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, which indicated the growth inhibition of MGC-803 cells via the induction of tumor cell apoptosis. Full article
(This article belongs to the Section Natural Products)
Open AccessCommunication Chiral Bis(Imidazolidine)Pyridine-Cu Complex-Catalyzed Enantioselective [3+2]-Cycloaddition of Azomethine Imines with Propiolates
Molecules 2012, 17(5), 6170-6178; doi:10.3390/molecules17056170
Received: 27 April 2012 / Revised: 18 May 2012 / Accepted: 21 May 2012 / Published: 24 May 2012
Cited by 25 | PDF Full-text (284 KB)
Abstract [3+2] Cycloaddition of azomethine imines with electron-deficient terminal alkynes was smoothly catalyzed by a chiral bis(imidazolidine)pyridine-CuOAc complex to give bicyclic pyrazolo[1,2-a]pyrazolone derivatives with up to 74% ee. Full article
(This article belongs to the Special Issue Asymmetric Catalysis)
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Review

Jump to: Research

Open AccessReview The Biological Effects of Ivabradine in Cardiovascular Disease
Molecules 2012, 17(5), 4924-4935; doi:10.3390/molecules17054924
Received: 17 January 2012 / Revised: 27 March 2012 / Accepted: 16 April 2012 / Published: 30 April 2012
Cited by 10 | PDF Full-text (178 KB)
Abstract
A large number of studies in healthy and asymptomatic subjects, as well as patients with already established cardiovascular disease (CAD) have demonstrated that heart rate (HR) is a very important and major independent cardiovascular risk factor for prognosis. Lowering heart rate reduces [...] Read more.
A large number of studies in healthy and asymptomatic subjects, as well as patients with already established cardiovascular disease (CAD) have demonstrated that heart rate (HR) is a very important and major independent cardiovascular risk factor for prognosis. Lowering heart rate reduces cardiac work, thereby diminishing myocardial oxygen demand. Several experimental studies in animals, including dogs and pigs, have clarified the beneficial effects of ivabradine associated with HR lowering. Ivabradine is a selective inhibitor of the hyperpolarisation activated cyclic-nucleotide-gated funny current (If) involved in pacemaker generation and responsiveness of the sino-atrial node (SAN), which result in HR reduction with no other apparent direct cardiovascular effects. Several studies show that ivabradine substantially and significantly reduces major risks associated with heart failure when added to guideline-based and evidence-based treatment. However the biological effect of ivabradine have yet to be studied. This effects can appear directly on myocardium or on a systemic level improving endothelial function and modulating immune cell migration. Indeed ivabradine is an ‘open-channel’ blocker of human hyperpolarization-activated cyclic nucleotide gated channels of type-4 (hHCN4), and a ‘closed-channel’ blocker of mouse HCN1 channels in a dose-dependent manner. At endothelial level ivabradine decreased monocyte chemotactin protein-1 mRNA expression and exerted a potent anti-oxidative effect through reduction of vascular NADPH oxidase activity. Finally, on an immune level, ivabradine inhibits the chemokine-induced migration of CD4-positive lymphocytes. In this review, we discuss the biological effects of ivabradine and highlight its effects on CAD. Full article
(This article belongs to the Special Issue Ivabradine)
Open AccessReview Hydrophilic Carotenoids: Recent Progress
Molecules 2012, 17(5), 5003-5012; doi:10.3390/molecules17055003
Received: 22 March 2012 / Revised: 17 April 2012 / Accepted: 19 April 2012 / Published: 30 April 2012
Cited by 3 | PDF Full-text (305 KB)
Abstract
Carotenoids are substantially hydrophobic antioxidants. Hydrophobicity is this context is rather a disadvantage, because their utilization in medicine as antioxidants or in food chemistry as colorants would require some water dispersibility for their effective uptake or use in many other ways. In [...] Read more.
Carotenoids are substantially hydrophobic antioxidants. Hydrophobicity is this context is rather a disadvantage, because their utilization in medicine as antioxidants or in food chemistry as colorants would require some water dispersibility for their effective uptake or use in many other ways. In the past 15 years several attempts were made to synthetize partially hydrophilic carotenoids. This review compiles the recently synthetized hydrophilic carotenoid derivatives. Full article
(This article belongs to the Special Issue Carotenoids)
Open AccessReview The Pharmacological Properties and Therapeutic Use of Apomorphine
Molecules 2012, 17(5), 5289-5309; doi:10.3390/molecules17055289
Received: 1 March 2012 / Revised: 22 April 2012 / Accepted: 25 April 2012 / Published: 7 May 2012
Cited by 19 | PDF Full-text (581 KB)
Abstract
Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D1, D2S, D2L, D3, D4, and D5 receptors (and is thus classified as a non-selective dopamine [...] Read more.
Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D1, D2S, D2L, D3, D4, and D5 receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT1A, 5HT2A, 5HT2B, and 5HT2C), and α-adrenergic receptors (α1B, α1D, α2A, α2B, and α2C). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (i.e., to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer’s disease has been suggested; APO seems to stimulate Ab catabolism in an animal model and cell culture, thus reducing the rate of Ab oligomerisation and consequent neural cell death. Full article
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Open AccessReview Solid-Phase Parallel Synthesis of Drug-Like Artificial 2H-Benzopyran Libraries
Molecules 2012, 17(5), 5467-5496; doi:10.3390/molecules17055467
Received: 10 April 2012 / Revised: 25 April 2012 / Accepted: 7 May 2012 / Published: 9 May 2012
Cited by 15 | PDF Full-text (433 KB)
Abstract
This review covers the construction of drug-like 2H-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di- and trisubstituted benzopyran derivatives and additional ring-fused benzopyrans such as benzopyranoisoxazoles, benzopyranopyrazoles, six-membered [...] Read more.
This review covers the construction of drug-like 2H-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di- and trisubstituted benzopyran derivatives and additional ring-fused benzopyrans such as benzopyranoisoxazoles, benzopyranopyrazoles, six-membered ring-fused benzopyrans, and polycyclic benzopyrans are highlighted. Full article
(This article belongs to the Special Issue Solid Phase Synthesis)
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Open AccessReview Fluorescent Nanoprobes Dedicated to in Vivo Imaging: From Preclinical Validations to Clinical Translation
Molecules 2012, 17(5), 5564-5591; doi:10.3390/molecules17055564
Received: 5 April 2012 / Revised: 6 May 2012 / Accepted: 7 May 2012 / Published: 10 May 2012
Cited by 56 | PDF Full-text (1095 KB)
Abstract
With the fast development, in the last ten years, of a large choice of set-ups dedicated to routine in vivo measurements in rodents, fluorescence imaging techniques are becoming essential tools in preclinical studies. Human clinical uses for diagnostic and image-guided surgery are [...] Read more.
With the fast development, in the last ten years, of a large choice of set-ups dedicated to routine in vivo measurements in rodents, fluorescence imaging techniques are becoming essential tools in preclinical studies. Human clinical uses for diagnostic and image-guided surgery are also emerging. In comparison to low-molecular weight organic dyes, the use of fluorescent nanoprobes can improve both the signal sensitivity (better in vivo optical properties) and the fluorescence biodistribution (passive “nano” uptake in tumours for instance). A wide range of fluorescent nanoprobes have been designed and tested in preclinical studies for the last few years. They will be reviewed and discussed considering the obstacles that need to be overcome for their potential everyday use in clinics. The conjugation of fluorescence imaging with the benefits of nanotechnology should open the way to new medical applications in the near future. Full article
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Open AccessReview Stimulatory Action of Cyclooxygenase Inhibitors on Hematopoiesis: A Review
Molecules 2012, 17(5), 5615-5625; doi:10.3390/molecules17055615
Received: 12 April 2012 / Revised: 4 May 2012 / Accepted: 8 May 2012 / Published: 10 May 2012
Cited by 7 | PDF Full-text (183 KB)
Abstract
The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts [...] Read more.
The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts the feedback to positive control. Based on these relationships, agents inhibiting cyclo-oxygenases, known as non-steroidal anti-inflammatory drugs (NSAIDs), can activate hematopoiesis and be protective or curative under myelosuppressive states. The effectiveness of therapeutic use of NSAIDs in these situations is expressive especially under the selective inhibition of cyclooxygenase-2 (COX-2), when undesirable side effects of cyclooxygenase-1 inhibition, like gastrointestinal damage, are absent. The effects of the clinically approved selective COX-2 inhibitor, meloxicam, were investigated and demonstrated significant hematopoiesis-stimulating and survival-enhancing actions of this drug in sublethally or lethally γ-irradiated mice. These effects were connected with the ability of meloxicam to increase serum levels of the granulocyte colony-stimulating factor. It can be inferred from these findings that selective COX-2 inhibitors might find their use in the treatment of myelosuppressions of various etiologies. Full article
Open AccessReview Effect of Some Biopolymers on the Rheological Behavior of Surimi Gel
Molecules 2012, 17(5), 5733-5744; doi:10.3390/molecules17055733
Received: 17 April 2012 / Revised: 8 May 2012 / Accepted: 9 May 2012 / Published: 14 May 2012
Cited by 3 | PDF Full-text (262 KB)
Abstract
The objective of this study was to investigate the effect of selected biopolymers on the rheological properties of surimi. In our paper, we highlight the functional properties and rheological aspects of some starch mixtures used in surimi. However, the influence of some [...] Read more.
The objective of this study was to investigate the effect of selected biopolymers on the rheological properties of surimi. In our paper, we highlight the functional properties and rheological aspects of some starch mixtures used in surimi. However, the influence of some other ingredients, such as cryoprotectants, mannans, and hydroxylpropylmethylcellulose (HPMC), on the rheological properties of surimi is also described. The outcome reveals that storage modulus increased with the addition of higher levels of starch. Moreover, the increasing starch level increased the breaking force, deformation, and gel strength of surimi as a result of the absorption of water by starch granules in the mixture to make the surimi more rigid. On the other hand, the addition of cryoprotectants, mannans, and HPMC improved the rheological properties of surimi. The data obtained in this paper could be beneficial particularly to the scientists who deal with food processing field. Full article
Open AccessReview Recent Advances in Photoinduced Electron Transfer Processes of Fullerene-Based Molecular Assemblies and Nanocomposites
Molecules 2012, 17(5), 5816-5835; doi:10.3390/molecules17055816
Received: 29 March 2012 / Revised: 3 May 2012 / Accepted: 8 May 2012 / Published: 16 May 2012
Cited by 67 | PDF Full-text (919 KB)
Abstract
Photosensitized electron-transfer processes of fullerenes hybridized with electron donating or other electron accepting molecules have been surveyed in this review on the basis of the recent results reported mainly from our laboratories. Fullerenes act as photo-sensitizing electron acceptors with respect to a [...] Read more.
Photosensitized electron-transfer processes of fullerenes hybridized with electron donating or other electron accepting molecules have been surveyed in this review on the basis of the recent results reported mainly from our laboratories. Fullerenes act as photo-sensitizing electron acceptors with respect to a wide variety of electron donors; in addition, fullerenes in the ground state also act as good electron acceptors in the presence of light-absorbing electron donors such as porphyrins. With single-wall carbon nanotubes (SWCNTs), the photoexcited fullerenes act as electron acceptor. In the case of triple fullerene/porphyrin/SWCNT architectures, the photoexcited porphyrins act as electron donors toward the fullerene and SWCNT. These mechanisms are rationalized with the molecular orbital considerations performed for these huge supramolecules. For the confirmation of the electron transfer processes, transient absorption methods have been used, in addition to time-resolved fluorescence spectral measurements. The kinetic data obtained in solution are found to be quite useful to predict the efficiencies of photovoltaic cells. Full article
(This article belongs to the Special Issue Fullerene Chemistry)
Open AccessReview Modifications on the Basic Skeletons of Vinblastine and Vincristine
Molecules 2012, 17(5), 5893-5914; doi:10.3390/molecules17055893
Received: 30 March 2012 / Revised: 9 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012
Cited by 18 | PDF Full-text (940 KB)
Abstract
The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the [...] Read more.
The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous efforts have been directed towards synthesizing new derivatives of the antitumor agents vinblastine and vincristine so as to obtain novel compounds with improved therapeutic properties. Full article
(This article belongs to the Special Issue Advances in Heteroaromatic Chemistry)
Open AccessReview Synthesis and Bioactivity of Secondary Metabolites from Marine Sponges Containing Dibrominated Indolic Systems
Molecules 2012, 17(5), 6083-6099; doi:10.3390/molecules17056083
Received: 20 April 2012 / Revised: 14 May 2012 / Accepted: 15 May 2012 / Published: 21 May 2012
Cited by 22 | PDF Full-text (293 KB)
Abstract
Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium cyaneum, Aplidium meridianum.) produce bioactive secondary metabolites involved in their defence mechanisms. Recently it was demonstrated that several of those compounds show a large variety of biological activities against [...] Read more.
Marine sponges. (e.g., Hyrtios sp., Dragmacidin sp., Aglophenia pleuma, Aplidium cyaneum, Aplidium meridianum.) produce bioactive secondary metabolites involved in their defence mechanisms. Recently it was demonstrated that several of those compounds show a large variety of biological activities against different human diseases with possible applications in medicinal chemistry and in pharmaceutical fields, especially related to the new drug development process. Researchers have focused their attention principally on secondary metabolites with anti-cancer and cytotoxic activities. A common target for these molecules is the cytoskeleton, which has a central role in cellular proliferation, motility, and profusion involved in the metastatic process associate with tumors. In particular, many substances containing brominated indolic rings such as 5,6-dibromotryptamine, 5,6-dibromo-N-methyltryptamine, 5,6-dibromo-N-methyltryptophan (dibromoabrine), 5,6-dibromo-N,N-dimethyltryptamine and 5,6-dibromo-L-hypaphorine isolated from different marine sources, have shown anti-cancer activity, as well as antibiotic and anti-inflammatory properties. Considering the structural correlation between endogenous monoamine serotonin with marine indolic alkaloids 5,6-dibromoabrine and 5,6-dibromotryptamine, a potential use of some dibrominated indolic metabolites in the treatment of depression-related pathologies has also been hypothesized. Due to the potential applications in the treatment of various diseases and the increasing demand of these compounds for biological assays and the difficult of their isolation from marine sources, we report in this review a series of recent syntheses of marine dibrominated indole-containing products. Full article
(This article belongs to the collection Bioactive Compounds)

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