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Molecules, Volume 16, Issue 12 (December 2011), Pages 9775-10721

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Open AccessArticle Fluorescence Resonance Energy Transfer Assay for High-Throughput Screening of ADAMTS1 Inhibitors
Molecules 2011, 16(12), 10709-10721; https://doi.org/10.3390/molecules161210709
Received: 4 November 2011 / Revised: 6 December 2011 / Accepted: 13 December 2011 / Published: 20 December 2011
Cited by 11 | PDF Full-text (417 KB)
Abstract
A disintegrin and metalloprotease with thrombospondin type I motifs-1 (ADAMTS1) plays a crucial role in inflammatory joint diseases and its inhibitors are potential candidates for anti-arthritis drugs. For the purposes of drug discovery, we reported the development and validation of fluorescence resonance energy
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A disintegrin and metalloprotease with thrombospondin type I motifs-1 (ADAMTS1) plays a crucial role in inflammatory joint diseases and its inhibitors are potential candidates for anti-arthritis drugs. For the purposes of drug discovery, we reported the development and validation of fluorescence resonance energy transfer (FRET) assay for high-throughput screening (HTS) of the ADAMTS1 inhibitors. A FRET substrate was designed for a quantitative assay of ADAMTS1 activity and enzyme kinetics studies. The assay was developed into a 50-µL, 384-well assay format for high throughput screening of ADAMTS1 inhibitors with an overall Z’ factor of 0.89. ADAMTS1 inhibitors were screened against a diverse library of 40,960 total compounds with the established HTS system. Four structurally related hits, naturally occurring compounds, kuwanon P, kuwanon X, albafuran C and mulberrofuran J, extracted from the Chinese herb Morus alba L., were identified for further investigation. The results suggest that this FRET assay is an excellent tool, not only for measurement of ADAMTS1 activity but also for discovery of novel ADAMTS1 inhibitors with HTS. Full article
Open AccessArticle Cleavage of Oligonucleotides Containing a P3’→N5’ Phosphoramidate Linkage Mediated by Single-Stranded Oligonucleotide Templates
Molecules 2011, 16(12), 10695-10708; https://doi.org/10.3390/molecules161210695
Received: 1 November 2011 / Revised: 9 December 2011 / Accepted: 13 December 2011 / Published: 20 December 2011
PDF Full-text (503 KB) | Supplementary Files
Abstract
Double-stranded DNA (dsDNA) templates can hybridize to and accelerate cleavage of oligonucleotides containing a P3’→N5’ phosphoramidate (P-N) linkage. This dsDNA-templated cleavage of P-N linkages could be due to conformational strain placed on the linkage upon triplex formation. To determine whether duplex formation also
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Double-stranded DNA (dsDNA) templates can hybridize to and accelerate cleavage of oligonucleotides containing a P3’→N5’ phosphoramidate (P-N) linkage. This dsDNA-templated cleavage of P-N linkages could be due to conformational strain placed on the linkage upon triplex formation. To determine whether duplex formation also induced conformational strain, we examined the reactivity of the oligonucleotides with a P-N linkage in the presence of single-stranded templates, and compared these reactions to those with dsDNA templates. P-N oligonucleotides that are cleaved upon duplex formation could be used as probes to detect single-stranded nucleic acids. Full article
(This article belongs to the Special Issue DNA-Templated Synthesis)
Open AccessArticle Novel Pyrazolo[3,4-d]pyrimidine Derivatives as Potential Antitumor Agents: Exploratory Synthesis, Preliminary Structure-Activity Relationships, and in Vitro Biological Evaluation
Molecules 2011, 16(12), 10685-10694; https://doi.org/10.3390/molecules161210685
Received: 20 November 2011 / Revised: 2 December 2011 / Accepted: 13 December 2011 / Published: 20 December 2011
Cited by 24 | PDF Full-text (364 KB)
Abstract
In a cell-based screen of novel anticancer agents, the hit compound 1a which bears a pyrazolo[3,4-d]pyrimidine scaffold exhibited high inhibitory activity against a panel of four different types of tumor cell lines. In particular, the IC50 for A549 cells was
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In a cell-based screen of novel anticancer agents, the hit compound 1a which bears a pyrazolo[3,4-d]pyrimidine scaffold exhibited high inhibitory activity against a panel of four different types of tumor cell lines. In particular, the IC50 for A549 cells was 2.24 µM, compared with an IC50 of 9.20 µM for doxorubicin, the positive control. Four synthetic routes of the key intermediate 3 of 1a were explored and 1a was prepared via route D on the gram scale for further research. Two analogs of 1a were synthesized and their preliminary structure-activity relationships were studied. Flow cytometric analysis revealed that compound 1a could significantly induce apoptosis in A549 cells in vitro at low micromolar concentrations. These results suggest that the target compound 1a and its analogs with the pyrazolo[3,4-d]pyrimidine scaffold might potentially constitute a novel class of anticancer agents, which requires further studies. Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Microwave-Assisted Synthesis of New N1,N4-Substituted Thiosemicarbazones
Molecules 2011, 16(12), 10668-10684; https://doi.org/10.3390/molecules161210668
Received: 5 October 2011 / Revised: 6 December 2011 / Accepted: 16 December 2011 / Published: 20 December 2011
Cited by 9 | PDF Full-text (257 KB)
Abstract
We present an efficient procedure for the synthesis of thirty-six N1,N4-substituted thiosemicarbazones, including twenty-five ones that are reported for the first time, using a microwave-assisted methodology for the reaction of thiosemicarbazide intermediates with aldehydes in the presence of
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We present an efficient procedure for the synthesis of thirty-six N1,N4-substituted thiosemicarbazones, including twenty-five ones that are reported for the first time, using a microwave-assisted methodology for the reaction of thiosemicarbazide intermediates with aldehydes in the presence of glacial acetic acid in ethanol and under solvent free conditions. Overall reaction times (20–40 min when ethanol as solvent, and 3 min under solvent free conditions) were much shorter than with the traditional procedure (480 min); satisfactory yields and high-purity compounds were obtained. The thiosemicarbazide intermediates were obtained from alkyl or aryl isothiocyanates and hydrazine hydrate or phenyl hydrazine by stirring at room temperature for 60 min or by microwave irradiation for 30 min, with lower yields for the latter. The preliminary in vitro antifungal activity of thiosemicarbazones was evaluated against Aspergillus parasiticus and Candida albicans. Full article
Open AccessArticle Resin Diterpenes from Austrocedrus chilensis
Molecules 2011, 16(12), 10653-10667; https://doi.org/10.3390/molecules161210653
Received: 11 November 2011 / Revised: 25 November 2011 / Accepted: 7 December 2011 / Published: 20 December 2011
Cited by 6 | PDF Full-text (501 KB)
Abstract
Seventeen diterpenes belonging to the labdane, abietane and isopimarane skeleton classes were isolated from the resin of the Chilean gymnosperm Austrocedrus chilensis and identified by spectroscopic and spectrometric methods. The diterpene 12-oxo-labda-8(17),13E-dien-19 oic acid is reported for the first time as
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Seventeen diterpenes belonging to the labdane, abietane and isopimarane skeleton classes were isolated from the resin of the Chilean gymnosperm Austrocedrus chilensis and identified by spectroscopic and spectrometric methods. The diterpene 12-oxo-labda-8(17),13E-dien-19 oic acid is reported for the first time as a natural product and 14 diterpenes are reported for the first time for the species. Full article
(This article belongs to the Section Natural Products Chemistry)
Open AccessArticle Four Eremophil-9-en-8-one Derivatives from Cremanthodium stenactinium Samples Collected in China
Molecules 2011, 16(12), 10645-10652; https://doi.org/10.3390/molecules161210645
Received: 22 November 2011 / Revised: 9 December 2011 / Accepted: 16 December 2011 / Published: 19 December 2011
Cited by 11 | PDF Full-text (262 KB)
Abstract
Two samples of Cremanthodium stenactinium (Asteraceae) were collected in Sichuan Province, China. From the ethyl acetate extracts of the roots, three new eremophilane-type sesquiterpenoids and one new trinoreremophilane compound were isolated, together with other known eremophilanes. Their structures were determined based on the
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Two samples of Cremanthodium stenactinium (Asteraceae) were collected in Sichuan Province, China. From the ethyl acetate extracts of the roots, three new eremophilane-type sesquiterpenoids and one new trinoreremophilane compound were isolated, together with other known eremophilanes. Their structures were determined based on the spectroscopic data. This is the first report of isolation of eremophilane-type compounds from the genus Cremanthodium. Full article
(This article belongs to the Special Issue Terpenoids)
Open AccessArticle Enhancement of Diosgenin Production in Dioscorea zingiberensis Cell Cultures by Oligosaccharides from Its Endophytic Fungus Fusarium oxysporum Dzf17
Molecules 2011, 16(12), 10631-10644; https://doi.org/10.3390/molecules161210631
Received: 16 November 2011 / Revised: 2 December 2011 / Accepted: 9 December 2011 / Published: 19 December 2011
Cited by 17 | PDF Full-text (203 KB) | Supplementary Files
Abstract
The effects of the oligosaccharides from the endophytic fungus Fusarium oxysporum Dzf17 as elicitors on diosgenin production in cell suspension cultures of its host Dioscorea zingiberensis were investigated. Three oligosaccharides, DP4, DP7 and DP10, were purified from the oligosaccharide fractions DP2-5, DP5-8 and
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The effects of the oligosaccharides from the endophytic fungus Fusarium oxysporum Dzf17 as elicitors on diosgenin production in cell suspension cultures of its host Dioscorea zingiberensis were investigated. Three oligosaccharides, DP4, DP7 and DP10, were purified from the oligosaccharide fractions DP2-5, DP5-8 and DP8-12, respectively, which were prepared from the water-extracted mycelial polysaccharide of the endophytic fungus F. oxysporum Dzf17. When the cell cultures were treated with fraction DP5-8 at 20 mg/L on day 26 and harvested on day 32, the maximum diosgenin yield (2.187 mg/L) was achieved, which was 5.65-fold of control (0.387 mg/L). When oligosaccharides DP4, DP7 and DP10 were individually added to 26-day-old D. zingiberensis cell cultures at concentrations of 2, 4, 6, 8 and 10 mg/L in medium, DP7 at 6 mg/L was found to significantly enhance diosgenin production, with a yield of 3.202 mg/L, which was 8.27-fold of control. When the cell cultures were treated with DP7 twice on days 24 and 26, and harvested on day 30, both diosgenin content and yield were significantly increased and reached the maximums of 1.159 mg/g dw and 4.843 mg/L, both of which were higher than those of single elicitation, and were 9.19- and 12.38-fold of control, respectively. Full article
(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)
Open AccessArticle The in Vitro Structure-Related Anti-Cancer Activity of Ginsenosides and Their Derivatives
Molecules 2011, 16(12), 10619-10630; https://doi.org/10.3390/molecules161210619
Received: 25 October 2011 / Revised: 9 December 2011 / Accepted: 16 December 2011 / Published: 19 December 2011
Cited by 44 | PDF Full-text (465 KB)
Abstract
Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE), protopanaxadiol (PPD)-type,
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Panax ginseng has long been used in Asia as a herbal medicine for the prevention and treatment of various diseases, including cancer. The current study evaluated the cytotoxic potency against a variety of cancer cells by using ginseng ethanol extracts (RSE), protopanaxadiol (PPD)-type, protopanaxatriol (PPT)-type ginsenosides fractions, and their hydrolysates, which were prepared by stepwise hydrolysis of the sugar moieties of the ginsenosides. The results showed that the cytotoxic potency of the hydrolysates of RSE and total PPD-type or PPT-type ginsenoside fractions was much stronger than the original RSE and ginsenosides; especially the hydrolysate of PPD-type ginsenoside fractions. Subsequently, two derivatives of protopanaxadiol (1), compounds 2 and 3, were synthesized via hydrogenation and dehydration reactions of compound 1. Using those two derivatives and the original ginsenosides, a comparative study on various cancer cell lines was conducted; the results demonstrated that the cytotoxic potency was generally in the descending order of compound 3 > 20(S)-dihydroprotopanaxadiol (2) > PPD (1) > 20(S)-Rh2 > 20(R)-Rh2 ≈ 20(R)-Rg3 ≈ 20(S)-Rg3. The results clearly indicate the structure-related activities in which the compound with less polar chemical structures possesses higher cytotoxic activity towards cancer cells. Full article
Open AccessReview Terpenoids from Endophytic Fungi
Molecules 2011, 16(12), 10604-10618; https://doi.org/10.3390/molecules161210604
Received: 13 November 2011 / Revised: 2 December 2011 / Accepted: 12 December 2011 / Published: 19 December 2011
Cited by 21 | PDF Full-text (283 KB)
Abstract
This work reviews the production of terpenoids by endophytic fungi and their biological activities, in period of 2006 to 2010. Sixty five sesquiterpenes, 45 diterpenes, five meroterpenes and 12 other terpenes, amounting to 127 terpenoids were isolated from endophytic fungi. Full article
(This article belongs to the Special Issue Terpenoids)
Open AccessArticle Global Chemical Composition and Antioxidant and Anti-Tuberculosis Activities of Various Extracts of Globularia alypum L. (Globulariaceae) Leaves
Molecules 2011, 16(12), 10592-10603; https://doi.org/10.3390/molecules161210592
Received: 3 October 2011 / Revised: 23 November 2011 / Accepted: 2 December 2011 / Published: 19 December 2011
Cited by 15 | PDF Full-text (258 KB)
Abstract
In this work, an evaluation of the biological activities of Globularia alypum L. extracts and their global chemical composition was realized. Extracts from G. alypum were obtained by two extraction methods. The composition of polyphenols (8.5–139.95 g gallic acid equivalent/Kg of dry mass),
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In this work, an evaluation of the biological activities of Globularia alypum L. extracts and their global chemical composition was realized. Extracts from G. alypum were obtained by two extraction methods. The composition of polyphenols (8.5–139.95 g gallic acid equivalent/Kg of dry mass), tannins (1.39–18.65 g catechin equivalent/Kg of dry mass), anthocyanins (8.17–70.69 mg cyanidin equivalent/Kg of dry mass) and flavonoids (0.31–19.28 g quercetin equivalent/Kg of dry mass) was evaluated. The samples were subjected to a screening for their antioxidant activities using the DPPH· and ABTS·+ assays. For the first time, the anti-tuberculosis activity (H37Rv) for G. alypum was tested against Mycobacterium tuberculosis. The strongest antioxidant activity was obtained for the methanol extract (IC50 = 15.58 ± 0.168 mg/L) and the best anti-tuberculosis activity was obtained for the petroleum ether extract (IC50 = 77 mg/L). We have found a positive correlation between the total phenolics content and the antioxidant activity R2 = 0.88 (DPPH·) and R2 = 0.97 (ABTS·+). We have found also a positive correlation between the flavonoid content and the antioxidant activity R2 = 0.91 (DPPH·) and R2 = 0.91 (ABTS·+). Full article
(This article belongs to the Section Medicinal Chemistry)
Open AccessArticle Comparison of A and B Starch Granules from Three Wheat Varieties
Molecules 2011, 16(12), 10570-10591; https://doi.org/10.3390/molecules161210570
Received: 24 November 2011 / Accepted: 29 November 2011 / Published: 19 December 2011
Cited by 53 | PDF Full-text (1729 KB) | Supplementary Files
Abstract
Three starches from the wheat varieties AK58, ZM18 and YZ4110 were separated into large (A) and small (B) granules, which were characterized structurally and evaluated for their functional properties. SEM results showed that the size of A-granules from ZM18 and YZ4110 were about
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Three starches from the wheat varieties AK58, ZM18 and YZ4110 were separated into large (A) and small (B) granules, which were characterized structurally and evaluated for their functional properties. SEM results showed that the size of A-granules from ZM18 and YZ4110 were about the same, but the sizes of A-granules and B-granules from AK58 were larger than those of ZM18 and YZ4110. FTIR spectra showed that all the samples exhibited a similar pattern, with seven main modes with maximum absorbance peaks near 3,500, 3,000, 1,600, 1,400, 1,000, 800, 500 cm−1. The B-granules of ZM18 and YZ4110 had less amylose content, although the difference among the total amylose contents of the three unfractionated starches was not significant. X-ray diffraction (XRD) patterns showed predominantly A-type crystallinity for all the starches. The A-granules showed sharper XRD patterns than the other starches. DSC analysis showed that the A-granules had broader ranges of gelatinization temperatures than the B-granules from the same wheat variety. The gelatinization enthalpy (ΔH) of A-granules was higher than that of B-granules. AK58 exhibited the smallest enthalpy, while ZM18 showed the largest enthalpy. In pasting tests, the A-granule starch of AK58 had higher peak, final and setback viscosity, lower breakdown and pasting temperature, and the B-granule starch and unfractionated starch of AK58 had lower peak, breakdown, final and setback viscosity and higher pasting temperature than ZM18 and YZ4110. Full article
(This article belongs to the Section Molecular Diversity)
Open AccessArticle The Effects of Artesunate on the Expression of EGFR and ABCG2 in A549 Human Lung Cancer Cells and a Xenograft Model
Molecules 2011, 16(12), 10556-10569; https://doi.org/10.3390/molecules161210556
Received: 31 October 2011 / Revised: 25 November 2011 / Accepted: 5 December 2011 / Published: 19 December 2011
Cited by 36 | PDF Full-text (433 KB)
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Clinical and laboratory studies have suggested that multi-targeting approaches against neoplastic cells could help to increase patient survival and might reduce the emergence of cells that are resistant to single-target
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Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Clinical and laboratory studies have suggested that multi-targeting approaches against neoplastic cells could help to increase patient survival and might reduce the emergence of cells that are resistant to single-target inhibitors. Artesunate (ART) is one of the most potent and rapidly acting antimalarial agents known, and it also exerts a profound cytotoxic activity toward cancer cells and reverses multi-drug resistance. In the present study, we found that artesunate inhibited NSCLC A549 cell growth and proliferation, induced apoptosis and suppressed tumor growth in a dose-dependent manner in A549 cells and a mouse xenograft model. Furthermore, artesunate down-regulated the expression of epidermal growth factor receptor (EGFR), Akt and ATP-binding cassette subfamily G member 2 (ABCG2) at the mRNA and protein levels in vitro and in vivo. In conclusion, artesunate is an effective anti-cancer drug that may enhance the effectiveness of other anticancer drugs and may reverse multi-drug resistance by suppressing the transcription of ABCG2, which inhibits drug efflux. Full article
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Open AccessArticle Biotransformation of (1S)-2-Carene and (1S)-3-Carene by Picea abies Suspension Culture
Molecules 2011, 16(12), 10541-10555; https://doi.org/10.3390/molecules161210541
Received: 4 November 2011 / Revised: 5 December 2011 / Accepted: 12 December 2011 / Published: 19 December 2011
Cited by 6 | PDF Full-text (235 KB)
Abstract
Biotransformation of (1S)-2-carene and (1S)-3-carene by Picea abies suspension culture led to the formation of oxygenated products. (1S)-2-Carene was transformed slowly and the final product was identified as (1S)-2-caren-4-one. On the other hand, the transformation
[...] Read more.
Biotransformation of (1S)-2-carene and (1S)-3-carene by Picea abies suspension culture led to the formation of oxygenated products. (1S)-2-Carene was transformed slowly and the final product was identified as (1S)-2-caren-4-one. On the other hand, the transformation of (1S)-3-carene was rapid and finally led to the formation of (1S)-3-caren-5-one and (1S)-2-caren-4-one as equally abundant major products. The time-course of the reaction indicates that some products abundant at the beginning of the reaction (e.g. (1S,3S,4R)-3,4-epoxycarane and (1R)-p-mentha-1(7),2-dien-8-ol) were consumed by a subsequent transformations. Thus, a precise selection of the biotransformation time may be used for a production of specific compounds. Full article
(This article belongs to the Special Issue Terpenoids)
Open AccessReview Transdermal Drug Delivery Enhancement by Compounds of Natural Origin
Molecules 2011, 16(12), 10507-10540; https://doi.org/10.3390/molecules161210507
Received: 11 November 2011 / Revised: 3 December 2011 / Accepted: 9 December 2011 / Published: 16 December 2011
Cited by 54 | PDF Full-text (327 KB)
Abstract
The transdermal route of administration offers an alternative pathway for systemic drug delivery with numerous advantages over conventional routes. Regrettably, the stratum corneum forms a formidable barrier that hinders the percutaneous penetration of most drugs, offering an important protection mechanism to the organism
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The transdermal route of administration offers an alternative pathway for systemic drug delivery with numerous advantages over conventional routes. Regrettably, the stratum corneum forms a formidable barrier that hinders the percutaneous penetration of most drugs, offering an important protection mechanism to the organism against entrance of possible dangerous exogenous molecules. Different types of penetration enhancers have shown the potential to reversibly overcome this barrier to provide effective delivery of drugs across the skin. Although certain chemical and physical skin penetration enhancers are already employed by the pharmaceutical industry in commercially available transdermal products, some skin penetration enhancers are associated with irritating and toxic effects. This emphasizes the need for the discovery of new, safe and effective skin penetration enhancers. Penetration enhancers from natural origin have become popular as they offer several benefits over their synthetic counterparts such as sustainable mass production from a renewable resource and lower cost depending on the type of extraction used. The aim of this article is to give a comprehensive summary of the results from scientific research conducted on skin penetration enhancers of natural origin. The discussions on these natural penetration enhancers have been organized into the following chemical classes: essential oils, terpenes, fatty acids and polysaccharides. Full article
(This article belongs to the Section Natural Products Chemistry)
Open AccessReview The Role of Carotenoids in Human Skin
Molecules 2011, 16(12), 10491-10506; https://doi.org/10.3390/molecules161210491
Received: 17 November 2011 / Revised: 3 December 2011 / Accepted: 8 December 2011 / Published: 16 December 2011
Cited by 40 | PDF Full-text (213 KB)
Abstract
The human skin, as the boundary organ between the human body and the environment, is under the constant influence of free radicals (FR), both from the outside in and from the inside out. Carotenoids are known to be powerful antioxidant substances playing an
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The human skin, as the boundary organ between the human body and the environment, is under the constant influence of free radicals (FR), both from the outside in and from the inside out. Carotenoids are known to be powerful antioxidant substances playing an essential role in the reactions of neutralization of FR (mainly reactive oxygen species ROS). Carotenoid molecules present in the tissue are capable of neutralizing several attacks of FR, especially ROS, and are then destroyed. Human skin contains carotenoids, such as α-, γ-, β-carotene, lutein, zeaxanthin, lycopene and their isomers, which serve the living cells as a protection against oxidation. Recent studies have reported the possibility to investigate carotenoids in human skin quickly and non-invasively by spectroscopic means. Results obtained from in-vivo studies on human skin have shown that carotenoids are vital components of the antioxidative protective system of the human skin and could serve as marker substances for the overall antioxidative status. Reflecting the nutritional and stress situation of volunteers, carotenoids must be administered by means of antioxidant-rich products, e.g., in the form of fruit and vegetables. Carotenoids are degraded by stress factors of any type, inter alia, sun radiation, contact with environmental hazards, illness, etc. The kinetics of the accumulation and degradation of carotenoids in the skin have been investigated. Full article
(This article belongs to the Special Issue Carotenoids)
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