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Molecules, Volume 21, Issue 8 (August 2016)

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Cover Story Methylxanthines are phytochemicals that have been included in the diet of human populations for a [...] Read more.
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Editorial

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Open AccessEditorial Special Issue: “Functional Dendrimers”
Molecules 2016, 21(8), 1035; doi:10.3390/molecules21081035
Received: 27 July 2016 / Accepted: 1 August 2016 / Published: 9 August 2016
Cited by 4 | PDF Full-text (162 KB) | HTML Full-text | XML Full-text
Abstract
This special issue entitled “Functional Dendrimers” focuses on the manipulation of at least six “critical nanoscale design parameters” (CNDPs) of dendrimers including: size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. These CNDPs collectively define properties of all “functional dendrimers”. This special issue
[...] Read more.
This special issue entitled “Functional Dendrimers” focuses on the manipulation of at least six “critical nanoscale design parameters” (CNDPs) of dendrimers including: size, shape, surface chemistry, flexibility/rigidity, architecture and elemental composition. These CNDPs collectively define properties of all “functional dendrimers”. This special issue contains many interesting examples describing the manipulation of certain dendrimer CNDPs to create new emerging properties and, in some cases, predictive nanoperiodic property patterns (i.e., dendritic effects). The systematic engineering of CNDPs provides a valuable strategy for optimizing functional dendrimer properties for use in specific applications. Full article
(This article belongs to the Special Issue Functional Dendrimers)

Research

Jump to: Editorial, Review

Open AccessArticle Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile Derivatives as Anticancer Agents
Molecules 2016, 21(8), 894; doi:10.3390/molecules21080894
Received: 28 May 2016 / Revised: 4 July 2016 / Accepted: 5 July 2016 / Published: 29 July 2016
Cited by 2 | PDF Full-text (2440 KB) | HTML Full-text | XML Full-text
Abstract
Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has
[...] Read more.
Herein, we report an environmentally friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl-8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-α)pyrimidine-6-carbonitrile derivatives. The in-vitro anticancer activities of these compounds were evaluated against four human tumor cell lines. Among all the synthesized derivatives, compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the highest GI50 value of 32.7 μM, 55.3 μM, 34.3 μM, 28.9 μM for MCF-7, K562, HeLa and PC-3 cancer cell lines respectively. A docking study of the newly synthesized compounds were performed, and the results showed good binding mode in the active site of thymidylate synthase enzyme. ADME properties of synthesized compounds were also studied and showed good drug like properties. Full article
(This article belongs to the Special Issue ECSOC-19)
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Open AccessArticle Green Tea Leaves Extract: Microencapsulation, Physicochemical and Storage Stability Study
Molecules 2016, 21(8), 940; doi:10.3390/molecules21080940
Received: 25 April 2016 / Revised: 11 July 2016 / Accepted: 12 July 2016 / Published: 26 July 2016
Cited by 2 | PDF Full-text (2702 KB) | HTML Full-text | XML Full-text
Abstract
Green tea polyphenols have been reported to possess many biological properties. Despite the many potential benefits of green tea extracts, their sensitivity to high temperature, pH and oxygen is a major disadvantage hindering their effective utilization in the food industry. Green tea leaves
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Green tea polyphenols have been reported to possess many biological properties. Despite the many potential benefits of green tea extracts, their sensitivity to high temperature, pH and oxygen is a major disadvantage hindering their effective utilization in the food industry. Green tea leaves from the Cameron Highlands Malaysia were extracted using supercritical fluid extraction (SFE). To improve the stability, green tea extracts were encapsulated by spray-drying using different carrier materials including maltodextrin (MD), gum arabic (GA) and chitosan (CTS) and their combinations at different ratios. Encapsulation efficiency, total phenolic content and antioxidant capacity were determined and were found to be in the range of 71.41%–88.04%, 19.32–24.90 (g GAE/100 g), and 29.52%–38.05% respectively. Further analysis of moisture content, water activity, hygroscopicity, bulk density and mean particles size distribution of the microparticles were carried out and the results ranged from; 2.31%–5.11%, 0.28–0.36, 3.22%–4.71%, 0.22–0.28 g/cm3 and 40.43–225.64 µm respectively. The ability of the microparticles to swell in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) was determined as 142.00%–188.63% and 207.55%–231.77%, respectively. Release of catechin polyphenol from microparticles in SIF was higher comparable to that of SGF. Storage stability of encapsulated catechin extracts under different temperature conditions was remarkably improved compared to non-encapsulated extract powder. This study showed that total catechin, total phenolic content (TPC) and antioxidant activity did not decrease significantly (p ≥ 0.05) under 4 °C storage conditions. The half-life study results were in the range of 35–60, 34–65 and 231–288 weeks at storage temperatures of 40 °C, 25 °C and 4 °C respectively, therefore, for improved shelf-life stability we recommend that microparticles should be stored at temperatures below 25 °C. Full article
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Open AccessArticle Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives
Molecules 2016, 21(8), 967; doi:10.3390/molecules21080967
Received: 28 June 2016 / Revised: 19 July 2016 / Accepted: 20 July 2016 / Published: 23 July 2016
PDF Full-text (753 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra
[...] Read more.
A simple synthetic route affording 27%–85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The 1H- and 13C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra. Full article
(This article belongs to the collection Heterocyclic Compounds)
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Open AccessArticle Indole Alkaloids from the Leaves of Nauclea officinalis
Molecules 2016, 21(8), 968; doi:10.3390/molecules21080968
Received: 25 June 2016 / Revised: 18 July 2016 / Accepted: 20 July 2016 / Published: 23 July 2016
Cited by 1 | PDF Full-text (1383 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids,
[...] Read more.
Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity
Molecules 2016, 21(8), 969; doi:10.3390/molecules21080969
Received: 19 May 2016 / Revised: 18 July 2016 / Accepted: 18 July 2016 / Published: 27 July 2016
Cited by 4 | PDF Full-text (5079 KB) | HTML Full-text | XML Full-text
Abstract
Twenty-four new hybrid analogues (1538) containing 7-chloro-4-aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized. Twelve of the new compounds were evaluated against 58 human cancer cell lines by the U.S. National Cancer Institute (NCI). Compounds 25, 30, 31
[...] Read more.
Twenty-four new hybrid analogues (1538) containing 7-chloro-4-aminoquinoline and 2-pyrazoline N-heterocyclic fragments were synthesized. Twelve of the new compounds were evaluated against 58 human cancer cell lines by the U.S. National Cancer Institute (NCI). Compounds 25, 30, 31, 36, and 37 showed significant cytostatic activity, with the most outstanding GI50 values ranging from 0.05 to 0.95 µM. The hybrid compounds (1538) were also evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. From the obtained results some structure–activity relationships were outlined. Full article
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Open AccessArticle Halichoblelide D, a New Elaiophylin Derivative with Potent Cytotoxic Activity from Mangrove-Derived Streptomyces sp. 219807
Molecules 2016, 21(8), 970; doi:10.3390/molecules21080970
Received: 23 May 2016 / Revised: 10 July 2016 / Accepted: 21 July 2016 / Published: 25 July 2016
Cited by 2 | PDF Full-text (559 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
During our search for interesting bioactive secondary metabolites from mangrove actinomycetes, the strain Streptomyces sp. 219807 which produced a high elaiophylin yield of 4486 mg/L was obtained. A new elaiophylin derivative, halichoblelide D (1), along with seven known analogues 2
[...] Read more.
During our search for interesting bioactive secondary metabolites from mangrove actinomycetes, the strain Streptomyces sp. 219807 which produced a high elaiophylin yield of 4486 mg/L was obtained. A new elaiophylin derivative, halichoblelide D (1), along with seven known analogues 28 was isolated and identified from the culture broth. Their chemical structures were determined by detailed analysis of 1D and 2D NMR and HRMS data. The absolute configuration of halichoblelide D (1) was confirmed by comparing the CD spectrum with those of the reported analogues. Compounds 17 exhibited potent cytotoxic activities against HeLa and MCF-7 cells with IC50 values ranging from 0.19 to 2.12 μM. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Quorum Sensing Inhibition and Structure–Activity Relationships of β-Keto Esters
Molecules 2016, 21(8), 971; doi:10.3390/molecules21080971
Received: 12 May 2016 / Revised: 19 July 2016 / Accepted: 21 July 2016 / Published: 25 July 2016
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Abstract
Traditional therapeutics to treat bacterial infections have given rise to multi-drug resistant pathogens, which pose a major threat to human and animal health. In several pathogens, quorum sensing (QS)—a cell-cell communication system in bacteria—controls the expression of genes responsible for pathogenesis, thus representing
[...] Read more.
Traditional therapeutics to treat bacterial infections have given rise to multi-drug resistant pathogens, which pose a major threat to human and animal health. In several pathogens, quorum sensing (QS)—a cell-cell communication system in bacteria—controls the expression of genes responsible for pathogenesis, thus representing a novel target in the fight against bacterial infections. Based on the structure of the autoinducers responsible for QS activity and other QS inhibitors, we hypothesize that β-keto esters with aryl functionality could possess anti-QS activity. A panel of nineteen β-keto ester analogs was tested for the inhibition of bioluminescence (a QS-controlled phenotype) in the marine pathogen Vibrio harveyi. Initial screening demonstrated the need of a phenyl ring at the C-3 position for antagonistic activity. Further additions to the phenyl ring with 4-substituted halo groups or a 3- or 4-substituted methoxy group resulted in the most active compounds with IC50 values ranging from 23 µM to 53 µM. The compounds additionally inhibit green fluorescent protein production by E. coli JB525. Evidence is presented that aryl β-keto esters may act as antagonists of bacterial quorum sensing by competing with N-acyl homoserine lactones for receptor binding. Expansion of the β-keto ester panel will enable us to obtain more insight into the structure–activity relationships needed to allow for the development of novel anti-virulence agents. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Immobilization of Chlamydomonas reinhardtii CLH1 on APTES-Coated Magnetic Iron Oxide Nanoparticles and Its Potential in the Production of Chlorophyll Derivatives
Molecules 2016, 21(8), 972; doi:10.3390/molecules21080972
Received: 25 June 2016 / Revised: 18 July 2016 / Accepted: 21 July 2016 / Published: 26 July 2016
Cited by 1 | PDF Full-text (2405 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recombinant Chlamydomonas reinhardtii chlorophyllase 1 (CrCLH1) that could catalyze chlorophyll hydrolysis to chlorophyllide and phytol in vitro was successfully expressed in Escherichia coli. The recombinant CrCLH1 was immobilized through covalent binding with a cubic (3-aminopropyl) triethoxysilane (APTES) coating on magnetic iron oxide
[...] Read more.
Recombinant Chlamydomonas reinhardtii chlorophyllase 1 (CrCLH1) that could catalyze chlorophyll hydrolysis to chlorophyllide and phytol in vitro was successfully expressed in Escherichia coli. The recombinant CrCLH1 was immobilized through covalent binding with a cubic (3-aminopropyl) triethoxysilane (APTES) coating on magnetic iron oxide nanoparticles (MIONPs), which led to markedly improved enzyme performance and decreased biocatalyst costs for potential industrial application. The immobilized enzyme exhibited a high immobilization yield (98.99 ± 0.91 mg/g of gel) and a chlorophyllase assay confirmed that the immobilized recombinant CrCLH1 retained enzymatic activity (722.3 ± 50.3 U/g of gel). Biochemical analysis of the immobilized enzyme, compared with the free enzyme, showed higher optimal pH and pH stability for chlorophyll-a hydrolysis in an acidic environment (pH 3–5). In addition, compared with the free enzyme, the immobilized enzyme showed higher activity in chlorophyll-a hydrolysis in a high temperature environment (50–60 °C). Moreover, the immobilized enzyme retained a residual activity of more than 64% of its initial enzyme activity after 14 cycles in a repeated-batch operation. Therefore, APTES-coated MIONP-immobilized recombinant CrCLH1 can be repeatedly used to lower costs and is potentially useful for the industrial production of chlorophyll derivatives. Full article
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Open AccessArticle Estrogen Receptor Signaling and the PI3K/Akt Pathway Are Involved in Betulinic Acid-Induced eNOS Activation
Molecules 2016, 21(8), 973; doi:10.3390/molecules21080973
Received: 8 June 2016 / Revised: 20 July 2016 / Accepted: 21 July 2016 / Published: 25 July 2016
Cited by 3 | PDF Full-text (2436 KB) | HTML Full-text | XML Full-text
Abstract
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with anti-inflammatory, antiviral and anti-cancer properties. Beneficial cardiovascular effects such as increased nitric oxide (NO) production through enhancement of endothelial NO synthase (eNOS) activity and upregulation of eNOS expression have been demonstrated for this
[...] Read more.
Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with anti-inflammatory, antiviral and anti-cancer properties. Beneficial cardiovascular effects such as increased nitric oxide (NO) production through enhancement of endothelial NO synthase (eNOS) activity and upregulation of eNOS expression have been demonstrated for this compound. In the present study, immortalized human EA.hy 926 endothelial cells were incubated for up to 1 h with 1–100 µM BA and with the phosphatidylinositol-3-kinase (PI3K) inhibitors LY294002 and wortmannin, or the estrogen receptor (ER) antagonist ICI 182,780. Phosphorylation status of eNOS and total eNOS protein were analyzed by Western blotting using a serine 1177 phosphosite-specific antibody. Bioactive NO production was assessed by determination of cGMP content in rat lung fibroblasts (RFL-6) reporter cells. Short-term incubation of EA.hy 926 cells with BA resulted in eNOS phosphorylation at the serine 1177 residue in a concentration- and time-dependent manner with a half-maximal effective concentration of 0.57 µM. This was associated with an enhanced production of NO. BA-induced eNOS phosphorylation and NO production was completely blocked by pretreatment with ICI 182,780, and was attenuated by pretreatment with the PI3K inhibitors wortmannin and LY294002. These results indicate that fast non-genomic effects of ER with downstream signaling through the PI3K/Akt pathway and consecutive eNOS phosphorylation at serine 1177 are involved in BA-induced eNOS activation. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Corynoline Isolated from Corydalis bungeana Turcz. Exhibits Anti-Inflammatory Effects via Modulation of Nfr2 and MAPKs
Molecules 2016, 21(8), 975; doi:10.3390/molecules21080975
Received: 1 May 2016 / Revised: 12 July 2016 / Accepted: 25 July 2016 / Published: 27 July 2016
Cited by 5 | PDF Full-text (3159 KB) | HTML Full-text | XML Full-text
Abstract
Corydalis bungeana Turcz. is an anti-inflammatory medicinal herb used widely in traditional Chinese medicine for upper respiratory tract infections. It is demonstrated that corynoline is its active anti-inflammatory component. The nuclear factor-erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and the mitogen-activated protein
[...] Read more.
Corydalis bungeana Turcz. is an anti-inflammatory medicinal herb used widely in traditional Chinese medicine for upper respiratory tract infections. It is demonstrated that corynoline is its active anti-inflammatory component. The nuclear factor-erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and the mitogen-activated protein kinase (MAPK) pathway play important roles in the regulation of inflammation. In this study, we investigated the potential anti-inflammatory mechanism of corynoline through modulation of Nfr2 and MAPKs. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore modulatory role of NO production and the activation of signaling proteins and transcription factors using nitrite assay, Western bloting and qPCR. Treatment with corynoline reduced production of nitric oxide (NO) and the protein and mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) Treatment also significantly increased the expression of Nrf2, quinone oxidoreductase 1 (NQO1) and hemeoxygenase-1 (HO-1) at the mRNA and protein levels, which demonstrated that corynoline may protect cells from inflammation through the Nrf2/ARE pathway In addition, corynoline suppressed the expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), at the mRNA and protein levels. Furthermore, molecular data revealed that corynoline inhibited lipopolysaccharide-stimulated phosphorylation of c-jun NH2-terminal kinase (JNK) and p38. Taken together, these results suggest that corynoline reduces the levels of pro-inflammatory mediators, such as iNOS, COX-2, TNF-α and IL-1β, by suppressing extracellular signal-regulated kinase 1/2 (ERK) and p38 phosphorylation in RAW264.7 cells, which is regulated by the Nrf2/ARE pathway. These findings reveal part of the molecular basis for the anti-inflammatory properties of corynoline. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Efficacy of Acetylshikonin in Preventing Obesity and Hepatic Steatosis in db/db Mice
Molecules 2016, 21(8), 976; doi:10.3390/molecules21080976
Received: 24 June 2016 / Revised: 20 July 2016 / Accepted: 25 July 2016 / Published: 28 July 2016
Cited by 5 | PDF Full-text (2753 KB) | HTML Full-text | XML Full-text
Abstract
Zicao (Lithospermum erythrorhizon) has been used in clinics as a traditional Chinese medicine for thousands of years. Acetylshikonin (AS) is the main ingredient of Zicao, Xinjiang, China. The objective of this study was to investigate the anti-obesity and anti-nonalcoholic fatty liver
[...] Read more.
Zicao (Lithospermum erythrorhizon) has been used in clinics as a traditional Chinese medicine for thousands of years. Acetylshikonin (AS) is the main ingredient of Zicao, Xinjiang, China. The objective of this study was to investigate the anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD) efficacy of AS in a model of spontaneous obese db/db mice. Mice were divided into Wild Type (WT) groups and db/db groups, which received no treatment or treatment with 100 mg/kg/day clenbuterol (CL) hydrochloride or 540 mg/kg/day AS by oral gavage for eight weeks. The results provided the evidence that AS prevented obesity and NAFLD including reduction in body weight, food efficiency ratio, serum triglyceride (TG) and free fatty acid (FFA) levels in db/db mice. Administration of AS markedly suppressed the levels of hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines in treated groups when compared with that of db/db groups. Further investigation of the lipid synthesis-related protein using Western blotting revealed that hepatic protein expression of sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthetase (FAS) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were significantly downregulated by AS treatment. These findings suggest that AS exerts anti-obesity and anti-NAFLD effects through the regulation of lipid metabolism and anti-inflammatory effects. Full article
(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)
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Open AccessArticle Efficient Double Suzuki Cross-Coupling Reactions of 2,5-Dibromo-3-hexylthiophene: Anti-Tumor, Haemolytic, Anti-Thrombolytic and Biofilm Inhibition Studies
Molecules 2016, 21(8), 977; doi:10.3390/molecules21080977
Received: 27 May 2016 / Revised: 20 July 2016 / Accepted: 20 July 2016 / Published: 27 July 2016
Cited by 1 | PDF Full-text (689 KB) | HTML Full-text | XML Full-text
Abstract
The present study describes several novel 2,5-biaryl-3-hexylthiophene derivatives (3ai) synthesized via a Pd(0)-catalyzed Suzuki cross-coupling reaction in moderate to good yields. The novel compounds were also analyzed for their anti-thrombolytic, haemolytic, and biofilm inhibition activities. In addition, the anti-tumor
[...] Read more.
The present study describes several novel 2,5-biaryl-3-hexylthiophene derivatives (3ai) synthesized via a Pd(0)-catalyzed Suzuki cross-coupling reaction in moderate to good yields. The novel compounds were also analyzed for their anti-thrombolytic, haemolytic, and biofilm inhibition activities. In addition, the anti-tumor activity was also evaluated in vitro for newly-synthesized compounds, where 3-hexyl-2,5-bis(4-(methylthio)phenyl)thiophene exhibited the best anti-tumor activity against 4T1 cells with IC50 value of 16 μM. Moreover, 2,5-bis(4-methylphenyl)-3-hexylthiophene showed the highest activity against MCF-7 cells with an IC50 value of 26.2 μM. On the other hand, the compound 2,5-bis(4-chloropheny)-3-hexylthiophene exhibited excellent biofilm inhibition activity. Furthermore, the compound 2,5-bis(3-chloro-4-fluorophenyl)-3-hexylthiophene also exhibited better anti-thrombolytic and hemolytic activity results as compared to the other newly-synthesized compounds. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2
Molecules 2016, 21(8), 978; doi:10.3390/molecules21080978
Received: 14 June 2016 / Revised: 19 July 2016 / Accepted: 25 July 2016 / Published: 27 July 2016
PDF Full-text (6888 KB) | HTML Full-text | XML Full-text
Abstract
Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial
[...] Read more.
Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice. Full article
(This article belongs to the Special Issue Diversity of Alkaloids)
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Open AccessArticle Lutein, a Natural Carotenoid, Induces α-1,3-Glucan Accumulation on the Cell Wall Surface of Fungal Plant Pathogens
Molecules 2016, 21(8), 980; doi:10.3390/molecules21080980
Received: 18 January 2016 / Revised: 21 July 2016 / Accepted: 25 July 2016 / Published: 28 July 2016
Cited by 1 | PDF Full-text (2842 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
α-1,3-Glucan, a component of the fungal cell wall, is a refractory polysaccharide for most plants. Previously, we showed that various fungal plant pathogens masked their cell wall surfaces with α-1,3-glucan to evade plant immunity. This surface accumulation of α-1,3-glucan was infection specific, suggesting
[...] Read more.
α-1,3-Glucan, a component of the fungal cell wall, is a refractory polysaccharide for most plants. Previously, we showed that various fungal plant pathogens masked their cell wall surfaces with α-1,3-glucan to evade plant immunity. This surface accumulation of α-1,3-glucan was infection specific, suggesting that plant factors might induce its production in fungi. Through immunofluorescence observations of fungal cell walls, we found that carrot (Daucus carota) extract induced the accumulation of α-1,3-glucan on germlings in Colletotrichum fioriniae, a polyphagous fungal pathogen that causes anthracnose disease in various dicot plants. Bioassay-guided fractionation of carrot leaf extract successfully identified two active substances that caused α-1,3-glucan accumulation in this fungus: lutein, a carotenoid widely distributed in plants, and stigmasterol, a plant-specific membrane component. Lutein, which had a greater effect on C. fioriniae, also induced α-1,3-glucan accumulation in other Colletotrichum species and in the phylogenetically distant rice pathogen Cochliobolus miyabeanus, but not in the rice pathogen Magnaporthe oryzae belonging to the same phylogenetic subclass as Colletotrichum. Our results suggested that fungal plant pathogens reorganize their cell wall components in response to specific plant-derived compounds, which these pathogens may encounter during infection. Full article
(This article belongs to the Section Metabolites)
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Open AccessCommunication N,N′-Bis(2-cyclohexylethyl)naphtho[2,3-b:6,7-b′]dithiophene Diimides: Effects of Substituents
Molecules 2016, 21(8), 981; doi:10.3390/molecules21080981
Received: 19 June 2016 / Revised: 22 July 2016 / Accepted: 23 July 2016 / Published: 28 July 2016
Cited by 4 | PDF Full-text (2326 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Naphtho[2,3-b:6,7-b′]dithiophene-4,5,9,10-tetracarboxylic diimide (NDTI) is a promising electron-deficient building block for n-type organic conductors, and the performance of NDTI-based field-effect transistors (FETs) is largely dependent on the substituents that alter the supramolecular organization in the solid state and, in turn,
[...] Read more.
Naphtho[2,3-b:6,7-b′]dithiophene-4,5,9,10-tetracarboxylic diimide (NDTI) is a promising electron-deficient building block for n-type organic conductors, and the performance of NDTI-based field-effect transistors (FETs) is largely dependent on the substituents that alter the supramolecular organization in the solid state and, in turn, the intermolecular orbital overlap. For this reason, the rational selection of substituent on imide nitrogen atoms and/or thiophene α-positions is the key to developing superior n-type organic semiconductors. We here report new NDTI derivatives having N-(2-cyclohexylethyl) groups. Despite their one-dimensional packing structures in the solid state regardless of the presence or absence of chlorine groups at the thiophene α-positions, their FETs show promising performance with electron mobilities higher than 0.1 cm2·V−1·s−1 under ambient conditions. We also discuss how the cyclohexylethyl groups affect the packing structure in comparison with analogous n-octyl derivatives having the same number of carbon atoms. Full article
(This article belongs to the Special Issue Functional Naphthalene Diimides: Synthesis and Applications)
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Open AccessArticle Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel
Molecules 2016, 21(8), 982; doi:10.3390/molecules21080982
Received: 8 June 2016 / Revised: 11 July 2016 / Accepted: 21 July 2016 / Published: 29 July 2016
Cited by 2 | PDF Full-text (3556 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2′-hydroxy-3,4,4′,5,6′-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its
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We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative (2) of 2′-hydroxy-3,4,4′,5,6′-pentamethoxychalcone (1), induced cytotoxicity of tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes through which PC2 exerts its cytotoxic activity and its antitumor potential, remain to be addressed. In the present work, we aimed to (i) characterize the effect of PC2 on mitotic progression and the underlying mechanism; and to (ii) explore this information to evaluate its ability to sensitize tumor cells to paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis-arrested cells showed collapsed mitotic spindles with randomly distributed chromosomes, and activated spindle assembly checkpoint. Live-cell imaging revealed that the compound induced a prolonged delay (up to 14 h) in mitosis, culminating in massive cell death by blebbing. Importantly, PC2 in combination with paclitaxel enhanced the effect on cell growth inhibition as determined by cell viability and proliferation assays. Our findings demonstrate that the cytotoxicity induced by PC2 is mediated through antimitotic activity as a result of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of cancer cells to paclitaxel encourage further validation of the clinical potential of this combination. Full article
(This article belongs to the Special Issue New Approaches to Counteract Drug Resistance in Cancer)
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Open AccessArticle Bioactive Molecule Prediction Using Extreme Gradient Boosting
Molecules 2016, 21(8), 983; doi:10.3390/molecules21080983
Received: 1 May 2016 / Revised: 19 July 2016 / Accepted: 22 July 2016 / Published: 28 July 2016
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Abstract
Following the explosive growth in chemical and biological data, the shift from traditional methods of drug discovery to computer-aided means has made data mining and machine learning methods integral parts of today’s drug discovery process. In this paper, extreme gradient boosting (Xgboost), which
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Following the explosive growth in chemical and biological data, the shift from traditional methods of drug discovery to computer-aided means has made data mining and machine learning methods integral parts of today’s drug discovery process. In this paper, extreme gradient boosting (Xgboost), which is an ensemble of Classification and Regression Tree (CART) and a variant of the Gradient Boosting Machine, was investigated for the prediction of biological activity based on quantitative description of the compound’s molecular structure. Seven datasets, well known in the literature were used in this paper and experimental results show that Xgboost can outperform machine learning algorithms like Random Forest (RF), Support Vector Machines (LSVM), Radial Basis Function Neural Network (RBFN) and Naïve Bayes (NB) for the prediction of biological activities. In addition to its ability to detect minority activity classes in highly imbalanced datasets, it showed remarkable performance on both high and low diversity datasets. Full article
(This article belongs to the collection Molecular Docking)
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Open AccessArticle Influences of Adhesion Variability on the “Living” Dynamics of Filamentous Bacteria in Microfluidic Channels
Molecules 2016, 21(8), 985; doi:10.3390/molecules21080985
Received: 20 May 2016 / Revised: 18 July 2016 / Accepted: 21 July 2016 / Published: 28 July 2016
Cited by 2 | PDF Full-text (2088 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microfabricated devices have increasingly incorporated bacterial cells for microscale studies and exploiting cell-based functions in situ. However, the role of surface interactions in controlling the bacterial cell behavior is not well understood. In this study, microfluidic substrates of varied bacterial-binding affinity were used
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Microfabricated devices have increasingly incorporated bacterial cells for microscale studies and exploiting cell-based functions in situ. However, the role of surface interactions in controlling the bacterial cell behavior is not well understood. In this study, microfluidic substrates of varied bacterial-binding affinity were used to probe the interaction-driven behavior of filamentous Escherichia coli. In particular, cell alignment under controlled shear flow as well as subsequent orientation and filamentation were compared between cells presenting distinct outer membrane phenotypes. We demonstrated that filaments retained position under flow, which allowed for dynamic single-cell monitoring with in situ elongation of over 100 μm for adherent cells. This maximum was not reached by planktonic cells and was, therefore, adhesion-dependent. The bound filaments initially aligned with flow under a range of flow rates and their continual elongation was traced in terms of length and growth path; analysis demonstrated that fimbriae-mediated adhesion increased growth rate, increased terminal length, as well as dramatically changed the adherent geometry, particularly buckling behavior. The effects to filament length and buckling were further exaggerated by the strongest, specificity-driven adhesion tested. Such surface-guided control of the elongation process may be valuable to yield interesting “living” filamentous structures in microdevices. In addition, this work may offer a biomedically relevant platform for further elucidation of filamentation as an immune-resistant morphology. Overall, this work should inspire broader exploration of microfabricated devices for the study and application of single bacterial cells. Full article
(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)
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Open AccessArticle A Well-Defined {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} Complex Catalyzed Hiyama Coupling of Aryl Bromides with Arylsilanes
Molecules 2016, 21(8), 987; doi:10.3390/molecules21080987
Received: 27 May 2016 / Revised: 13 July 2016 / Accepted: 15 July 2016 / Published: 29 July 2016
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Abstract
A palladium (II) complex {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} catalyzed Hiyama cross-coupling reaction between aryl bromides and arylsilanes has been developed. The substituted biaryls were produced in moderate to high yields, regardless of electron-withdrawing or electron-donating. Full article
(This article belongs to the Special Issue Palladium Catalysts 2016)
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Open AccessArticle Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy Lactone
Molecules 2016, 21(8), 988; doi:10.3390/molecules21080988
Received: 28 June 2016 / Revised: 21 July 2016 / Accepted: 23 July 2016 / Published: 29 July 2016
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Abstract
Chiral epoxides—such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)-1a/1b)—are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation) in low to
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Chiral epoxides—such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)-1a/1b)—are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation) in low to moderate overall yield (20%–50%). Moreover, this procedure requires some harmful reagents such as sodium nitrite ((eco)toxic) and borane (carcinogen). Herein, starting from levoglucosenone (LGO), a biobased chiral compound obtained through the flash pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo-enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation, palladium-catalyzed hydrogenation, tosylation and treatment with sodium ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S)-3-(oxiran-2-yl)propanoates in 57% overall yield, respectively. To demonstrate the potentiality of this new synthetic pathway from LGO, the synthesis of high value-added (S)-dairy lactone was undertaken from these epoxides and provided the target in 37% overall yield from LGO. Full article
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Open AccessArticle Selective Extraction of Flavonoids from Sophora flavescens Ait. by Mechanochemistry
Molecules 2016, 21(8), 989; doi:10.3390/molecules21080989
Received: 9 June 2016 / Revised: 15 July 2016 / Accepted: 22 July 2016 / Published: 29 July 2016
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Abstract
Flavonoids from Sophora flavescens were selectively extracted by mechanochemical-promoted extraction technology (MPET) after using response surface methodology to determine the optimal extraction parameters. The highest yield of 35.17 mg/g was achieved by grinding the roots with Na2CO3 (15%) at 440
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Flavonoids from Sophora flavescens were selectively extracted by mechanochemical-promoted extraction technology (MPET) after using response surface methodology to determine the optimal extraction parameters. The highest yield of 35.17 mg/g was achieved by grinding the roots with Na2CO3 (15%) at 440 rpm/min for 17.0 min and water was used as the sole solvent with a ratio of solvent to solid material of 25 mL/g. Flavonoids prepared by MPET demonstrated relatively higher antioxidant activities in subsequent DPPH and hydroxyl radical scavenging assays. Main constituents in the extracts, including kurarinol, kushenol I/N and kurarinone, were characterized by HPLC-MS/MS, indicating good selective extraction by MPET. Physicochemical property changes of powder during mechanochemical milling were identified by scanning electron microscopy, X-ray powder diffraction, and UV-Vis diffuse-reflectance spectroscopy. Compared with traditional extraction methods, MPET possesses notable advantages of higher selectivity, lower extraction temperature, shorter extraction time, and organic solvent free properties. Full article
(This article belongs to the Special Issue Mechanochemistry)
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Open AccessArticle Isolation of a Cyclic (Alkyl)(amino)germylene
Molecules 2016, 21(8), 990; doi:10.3390/molecules21080990
Received: 7 July 2016 / Revised: 25 July 2016 / Accepted: 26 July 2016 / Published: 29 July 2016
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Abstract
A 1,4-addition of a dichlorogermylene dioxane complex with α,β-unsaturated imine 1 gave a dichlorogermane derivative 2 bearing a GeC3N five-membered ring skeleton. By reducing 2 with KC8, cyclic (alkyl)(amino)germylene 3 was synthesized and fully characterized. Germylene 3 readily reacted
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A 1,4-addition of a dichlorogermylene dioxane complex with α,β-unsaturated imine 1 gave a dichlorogermane derivative 2 bearing a GeC3N five-membered ring skeleton. By reducing 2 with KC8, cyclic (alkyl)(amino)germylene 3 was synthesized and fully characterized. Germylene 3 readily reacted with TEMPO, N2O and S8, producing the 1:2 adduct 4, the oxo-bridged dimer 5 and the sulfido-bridged dimer 6, respectively. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues
Molecules 2016, 21(8), 992; doi:10.3390/molecules21080992
Received: 6 June 2016 / Revised: 8 July 2016 / Accepted: 12 July 2016 / Published: 29 July 2016
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Abstract
Two spirosteroid analogues were synthesized and evaluated for their in vitro neuroprotective activities in PC12 cells, against glutamate-induced excitotoxicity and mitochondrial damage in glucose deprivation conditions, as well as their anti-inflammatory potential in LPS/IFNγ-stimulated microglia primary cultures. We also evaluated the in vitro
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Two spirosteroid analogues were synthesized and evaluated for their in vitro neuroprotective activities in PC12 cells, against glutamate-induced excitotoxicity and mitochondrial damage in glucose deprivation conditions, as well as their anti-inflammatory potential in LPS/IFNγ-stimulated microglia primary cultures. We also evaluated the in vitro anti-excitotoxic and anti-inflammatory activities of natural and endogenous steroids. Our results show that the plant-derived steroid solasodine decreased PC12 glutamate-induced excitotoxicity, but not the cell death induced by mitochondrial damage and glucose deprivation. Among the two synthetic spirosteroid analogues, only the (25R)-5α-spirostan-3,6-one (S15) protected PC12 against ischemia-related in vitro models and inhibited NO production, as well as the release of IL-1β by stimulated primary microglia. These findings provide further insights into the role of specific modifications of the A and B rings of sapogenins for their neuroprotective potential. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Chemical Composition and Inhibitory Effect of Lentinula edodes Ethanolic Extract on Experimentally Induced Atopic Dermatitis in Vitro and in Vivo
Molecules 2016, 21(8), 993; doi:10.3390/molecules21080993
Received: 27 May 2016 / Revised: 23 July 2016 / Accepted: 25 July 2016 / Published: 29 July 2016
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Abstract
The ethanolic extract of Lentinula edodes was partially analyzed and then characterized for its efficacy in treating atopic dermatitis. Polyphenols were determined to be the major antioxidant component in the extract (6.12 mg/g), followed by flavonoids (1.76 mg/g), β-carotene (28.75 μg/g), and lycopene
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The ethanolic extract of Lentinula edodes was partially analyzed and then characterized for its efficacy in treating atopic dermatitis. Polyphenols were determined to be the major antioxidant component in the extract (6.12 mg/g), followed by flavonoids (1.76 mg/g), β-carotene (28.75 μg/g), and lycopene (5.25 μg/g). An atopic dermatitis (AD) model was established and epidermal and dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels were measured after oral administration of the L. edodes extract for 4 weeks. L. edodes extract decreased Dermatophagoides farinae extract (DFE) and 4-dinitrochlorobenzene (DNCB)-induced expression of several inflammatory cytokines in the ears, cervical lymph nodes, and splenocytes. Consequently, L. edodes extract may have therapeutic potential in the treatment of AD attributable to its immunomodulatory effects. Full article
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Open AccessArticle Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies
Molecules 2016, 21(8), 995; doi:10.3390/molecules21080995
Received: 6 June 2016 / Revised: 15 July 2016 / Accepted: 18 July 2016 / Published: 30 July 2016
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Abstract
Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo
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Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma (BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma (MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly active against the majority of cells examined, with no significant impact on healthy lymphocytes. These active HAs induced caspase-dependent apoptosis, causing significant deregulation of several apoptosis-regulating proteins. Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak and survivin proteins. In conclusion, some of the HAs are potent tumor-selective inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro. Further preclinical studies of these agents are recommended. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Antioxidant Capacities of Fractions of Bamboo Shaving Extract and Their Antioxidant Components
Molecules 2016, 21(8), 996; doi:10.3390/molecules21080996
Received: 21 June 2016 / Revised: 27 July 2016 / Accepted: 27 July 2016 / Published: 30 July 2016
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Abstract
This research was conducted for evaluation of antioxidant activities of four fractions from bamboo shavings extract (BSE) and their antioxidant components. The antioxidant capacities of BSE and four fractions on ABTS, DPPH, FRAP and total antioxidant capacity assays exhibited the following descending order:
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This research was conducted for evaluation of antioxidant activities of four fractions from bamboo shavings extract (BSE) and their antioxidant components. The antioxidant capacities of BSE and four fractions on ABTS, DPPH, FRAP and total antioxidant capacity assays exhibited the following descending order: DF > n-butanol fraction (BF) > BSE ≈ ethyl acetate fraction (AF) > water fraction (WF). Among the identified phenolic compounds, caffeic acid exhibited the highest antioxidant capacities on DPPH, FRAP and total antioxidant capacity assays. An extremely significant positive correlation between the antioxidant activities with the contents of total flavonoids, total phenolic acids, or total phenolics was observed in this study. The result indicated that the bamboo shaving extract and its solvent fractions could act as natural antioxidants in light of their potent antioxidant activities. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Potential Application of p-Coumaric Acid on Differentiation of C2C12 Skeletal Muscle and 3T3-L1 Preadipocytes—An in Vitro and in Silico Approach
Molecules 2016, 21(8), 997; doi:10.3390/molecules21080997
Received: 22 June 2016 / Revised: 26 July 2016 / Accepted: 27 July 2016 / Published: 2 August 2016
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Abstract
Coumaric acid (CA) is a phenolic acid of the hydroxycinnamic acid family, and it has many biological functions such as anti-oxidant, anti-inflammatory, antidiabetic, anti-ulcer, anti-platelet, anti-cancer activities, etc. In the present study, we planned to analyse the potential molecular function of CA on
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Coumaric acid (CA) is a phenolic acid of the hydroxycinnamic acid family, and it has many biological functions such as anti-oxidant, anti-inflammatory, antidiabetic, anti-ulcer, anti-platelet, anti-cancer activities, etc. In the present study, we planned to analyse the potential molecular function of CA on skeletal muscle and preadipocytes differentiation using PCR and Western blot techniques. First, we analysed the impact of CA on C2C12 skeletal muscle differentiation. It revealed that CA treatment inhibited horse serum-induced skeletal muscle differentiation as evidenced by the decreased expression of early myogenic differentiation markers such as Myogenin and myoD via the AMP activated protein kinase- alpha AMPK-α mediated pathway. Furthermore, the level of lipid accumulation and changes in genes and protein expressions that are associated with lipogenesis and lipolysis were analyzed in 3T3-L1 cells. The Oil Red O staining evidenced that CA treatment inhibited lipid accumulation at the concentration of 0.1 and 0.2 mM. Furthermore, coumaric acid treatment decreased the expression of main transcriptional factors such as CCAAT/enhancer binding protein-alpha (C/EBP-α) and peroxisome proliferator-activated receptor gamma-2 (PPAR-γ2). Subsequently, CA treatment decreased the expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and adiponectin. Finally, we identified conformational changes induced by CA in PPAR-γ2 using computational biology tools. It revealed that CA might downregulate the PPAR-γ2 expression by directly binding with amino acids of PPAR-γ2 by hydrogen at 3.26 distance and hydrophobic interactions at 3.90 contact distances. These data indicated that CA suppressed skeletal muscle and preadipocytes differentiation through downregulation of the main transcriptional factors and their downstream targets. Full article
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Open AccessArticle Agavins Increase Neurotrophic Factors and Decrease Oxidative Stress in the Brains of High-Fat Diet-Induced Obese Mice
Molecules 2016, 21(8), 998; doi:10.3390/molecules21080998
Received: 12 April 2016 / Revised: 18 July 2016 / Accepted: 26 July 2016 / Published: 2 August 2016
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Abstract
Background: Fructans obtained from agave, called agavins, have recently shown significant benefits for human health including obesity. Therefore, we evaluated the potential of agavins as neuroprotectors and antioxidants by determining their effect on brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as
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Background: Fructans obtained from agave, called agavins, have recently shown significant benefits for human health including obesity. Therefore, we evaluated the potential of agavins as neuroprotectors and antioxidants by determining their effect on brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) as well as oxidative brain damage in of obese mice. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated daily with 5% (HFD/A5) or 10% (HFD/A10) of agavins or a standard diet (SD) for 10 weeks. The levels of BDNF and GDNF were evaluated by ELISA. The oxidative stress was evaluated by lipid peroxidation (TBARS) and carbonyls. SCFAs were also measured with GC-FID. Differences between groups were assessed using ANOVA and by Tukey’s test considering p < 0.05. Results: The body weight gain and food intake of mice HFD/A10 group were significantly lower than those in the HFD group. Agavins restored BDNF levels in HFD/A5 group and GDNF levels of HFD/A5 and HFD/A10 groups in cerebellum. Interestingly, agavins decreased TBARS levels in HFD/A5 and HFD/A10 groups in the hippocampus, frontal cortex and cerebellum. Carbonyl levels were also lower in HFD/A5 and HFD/A10 for only the hippocampus and cerebellum. It was also found that agavins enhanced SCFAs production in feces. Conclusion: Agavins may act as bioactive ingredients with antioxidant and protective roles in the brain. Full article
(This article belongs to the collection Advances in Carbohydrate Chemistry)
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Open AccessArticle Intramolecular Chain Hydrosilylation of Alkynylphenylsilanes Using a Silyl Cation as a Chain Carrier
Molecules 2016, 21(8), 999; doi:10.3390/molecules21080999
Received: 9 July 2016 / Revised: 25 July 2016 / Accepted: 27 July 2016 / Published: 1 August 2016
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Abstract
Diorganyl[2-(trimethylsilylethynyl)phenyl]silanes 1ac and methyl-substituted phenylsilanes 1d and 1e were treated with a small amount of trityl tetrakis(pentafluorophenyl)borate (TPFPB) as an initiator in benzene to afford the corresponding benzosiloles (2ae) in moderate to good yields. However, no reaction
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Diorganyl[2-(trimethylsilylethynyl)phenyl]silanes 1ac and methyl-substituted phenylsilanes 1d and 1e were treated with a small amount of trityl tetrakis(pentafluorophenyl)borate (TPFPB) as an initiator in benzene to afford the corresponding benzosiloles (2ae) in moderate to good yields. However, no reaction was observed for the reaction using [2-(1-hexynyl)phenyl]diisopropylsilane lf. The methyl substituent was tolerated under the reaction conditions and increased the yield of the corresponding benzosilole depending on the substitution position. From the result using 1f, the current reaction was found to require the trimethylsilyl group, which can stabilize intermediary alkenyl carbocations by the β-silyl effect. The current reaction can be considered an intramolecular chain hydrosilylation of alkynylarylsilanes involving silyl cations as chain carriers. Therefore, the silyl cations generated by hydride abstraction from hydrosilanes 1 with the trityl cation causes intramolecular electrophilic addition to the C-C triple bond to form ethenyl cations, which abstract a hydride from 1 to afford benzosiloles 2 with the regeneration of the silyl cations. Full article
(This article belongs to the Special Issue Advances in Silicon Chemistry)
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Open AccessArticle A General Catalytic Enantioselective Transfer Hydrogenation Reaction of β,β-Disubstituted Nitroalkenes Promoted by a Simple Organocatalyst
Molecules 2016, 21(8), 1000; doi:10.3390/molecules21081000
Received: 28 June 2016 / Revised: 15 July 2016 / Accepted: 28 July 2016 / Published: 30 July 2016
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Abstract
Given its synthetic relevance, the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes has received a great deal of attention. Several bio-, metal-, and organo-catalytic methods have been developed, which however are usually applicable to single classes of nitroalkene substrates. In this paper, we present
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Given its synthetic relevance, the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes has received a great deal of attention. Several bio-, metal-, and organo-catalytic methods have been developed, which however are usually applicable to single classes of nitroalkene substrates. In this paper, we present an account of our previous work on this transformation, which implemented with new disclosures and mechanistic insights results in a very general protocol for nitroalkene reductions. The proposed methodology is characterized by (i) a remarkably broad scope encompassing various nitroalkene classes; (ii) Hantzsch esters as convenient (on a preparative scale) hydrogen surrogates; (iii) a simple and commercially available thiourea as catalyst; (iv) user-friendly procedures. Overall, the proposed protocol gives a practical dimension to the catalytic enantioselective reduction of β,β-disubstituted nitroalkenes, offering a useful and general platform for the preparation of nitroalkanes bearing a stereogenic center at the β-position in a highly enantioenriched form. A transition state model derived from control kinetic experiments combined with literature data is proposed and discussed. This model accounts and justifies the observed experimental results. Full article
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Open AccessArticle The in Vitro and in Vivo Antitumor Activities of Tetracyclic Triterpenoids Compounds Actein and 26-Deoxyactein Isolated from Rhizome of Cimicifuga foetida L.
Molecules 2016, 21(8), 1001; doi:10.3390/molecules21081001
Received: 7 July 2016 / Revised: 23 July 2016 / Accepted: 27 July 2016 / Published: 30 July 2016
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Abstract
Aims: This work aims to study the in vitro and in vivo antitumor activities of tetracyclic triterpenoids compounds actein and 26-deoxyactein. Further, the mechanism is investigated. Methods: In vitro, a modified MTT method was used to assay the cytotoxicities of actein and 26-deoxyactein
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Aims: This work aims to study the in vitro and in vivo antitumor activities of tetracyclic triterpenoids compounds actein and 26-deoxyactein. Further, the mechanism is investigated. Methods: In vitro, a modified MTT method was used to assay the cytotoxicities of actein and 26-deoxyactein in 12 human tumor cell lines. In vivo, mouse sarcoma S180 and human lung cancer A549 cells were respectively implanted subcutaneously in ICR mice and nude mice to establish implanted tumor models. Flow cytometry (FCM) was used to assay the cycle distribution of the tumor cells. Immunohistochemistry was used to measure CD31-positive expression in the xenogrft tumor by analyzing microvessel density (MVD). In addition, acute toxicities of actein and 26-deoxyactein were also evaluated. Results: Actein and 26-deoxyactein inhibited the proliferation of the 12 human cancer cell lines tested with the values of 50% inhibitory concentrations (IC50) between 12.29 and 88.39 μg/mL. In vivo, both actein (3–27 mg/kg) and 26-deoxyactein (3–27 mg/kg) significantly inhibited the growth of the implanted sarcoma S180 in a dose-dependent manner. Actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) markedly inhibited the xenograft growth with T/C (%) values of 38%, 55% for actein, and 35%, 49% for 26-deoxyactein. Compared with the vehicle control, actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) significantly reduced the MVD in the xenograft tumor. The FCM result showed that human leukemia HL-60 cells were arrested at G1 phase after treated with either actein (6.25–25 μg/mL) or 26-deoxyactein (6.25–25 μg/mL) for 48 h. A limited trial in mice showed that both of the minimal lethal doses (MLDs) of actein and 26-deoxyactein were over 5 g/kg. Conclusions: Both actein and 26-deoxyactein have low toxicities. Importantly, both these two tetracyclic triterpenoids compounds isolated from rhizome of Cimicifuga foetida L. have significant antitumor activities in vitro and in vivo, which is associated with cell cycle arrest and angiogenesis inhibition. Full article
(This article belongs to the Section Natural Products)
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Open AccessFeature PaperArticle In Vivo Monitoring of the Growth of Fertilized Eggs of Medaka Fish (Oryzias latipes) by Near-Infrared Spectroscopy and Near-Infrared Imaging—A Marked Change in the Relative Content of Weakly Hydrogen-Bonded Water in Egg Yolk Just before Hatching
Molecules 2016, 21(8), 1003; doi:10.3390/molecules21081003
Received: 14 May 2016 / Revised: 21 July 2016 / Accepted: 27 July 2016 / Published: 1 August 2016
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Abstract
The present study develops further our previous study of in vivo monitoring at the molecular level of the embryonic development in Japanese medaka fish (Oryzias latipes) using near-infrared (NIR) spectroscopy and NIR imaging. NIR spectra were measured nondestructively for three major
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The present study develops further our previous study of in vivo monitoring at the molecular level of the embryonic development in Japanese medaka fish (Oryzias latipes) using near-infrared (NIR) spectroscopy and NIR imaging. NIR spectra were measured nondestructively for three major parts of fertilized medaka eggs (the embryonic body, oil droplets, and egg yolk) from the first day after fertilization to the day just before hatching (JBH). Changes in the contents of chemical components such as proteins, water, and lipids were monitored in situ during embryonic development. A marked change in the relative content of weakly hydrogen-bonded water was observed in the egg yolk JBH. Principal component analysis (PCA) was carried out using the NIR spectra data of the egg yolk and embryo on the fifth day after fertilization. The PCA clearly separates the egg yolk data from the embryo body parts. Principal component PC1 and PC2 loading plots suggest that the hydrogen bonding structure of water in the egg yolk is considerably different to those of the other parts and the fraction of weakly hydrogen-bonded water in the egg yolk is smaller than that in the embryonic body. NIR images developed from the intensities of peaks of second derivative spectra owing to water and proteins show their different distribution patterns. Images of the ratio of strongly and weakly hydrogen-bonded water confirmed that oil droplets and embryonic body parts have higher and lower ratios, respectively, of strongly hydrogen-bonded water than do the other parts. The images developed from the intensity of the peaks at 4864 and 4616 cm−1 related to the proteins indicated that the egg yolk contains a higher concentration of protein than do the other parts. The peaks at 5756 and 4530 cm−1 caused by the protein secondary structures of α-helix and β-sheet showed the configuration of the egg cell membrane. The present study might lead to new understanding at the molecular level regarding the growth of fertilized eggs and provides a new tool to visualize egg development in a nondestructive manner. Full article
(This article belongs to the Special Issue Vibrational Spectroscopic Imaging and Mapping)
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Open AccessArticle Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents
Molecules 2016, 21(8), 1004; doi:10.3390/molecules21081004
Received: 24 June 2016 / Revised: 26 July 2016 / Accepted: 28 July 2016 / Published: 1 August 2016
Cited by 5 | PDF Full-text (2402 KB) | HTML Full-text | XML Full-text
Abstract
In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively.
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In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments. Full article
(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)
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Open AccessArticle Preparation of Hydrochlorothiazide Nanoparticles for Solubility Enhancement
Molecules 2016, 21(8), 1005; doi:10.3390/molecules21081005
Received: 1 June 2016 / Revised: 25 July 2016 / Accepted: 29 July 2016 / Published: 2 August 2016
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Abstract
Nanoparticles can be considered as a useful tool for improving properties of poorly soluble active ingredients. Hydrochlorothiazide (Class IV of the Biopharmaceutical Classification System) was chosen as a model compound. Antisolvent precipitation-solvent evaporation and emulsion solvent evaporation methods were used for preparation of
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Nanoparticles can be considered as a useful tool for improving properties of poorly soluble active ingredients. Hydrochlorothiazide (Class IV of the Biopharmaceutical Classification System) was chosen as a model compound. Antisolvent precipitation-solvent evaporation and emulsion solvent evaporation methods were used for preparation of 18 samples containing hydrochlorothiazide nanoparticles. Water solutions of surfactants sodium dodecyl sulfate, Tween 80 and carboxymethyl dextran were used in mass concentrations of 1%, 3% and 5%. Acetone and dichloromethane were used as solvents of the model compound. The particle size of the prepared samples was measured by dynamic light scattering. The selected sample of hydrochlorothiazide nanoparticles stabilized with carboxymethyl dextran sodium salt with particle size 2.6 nm was characterized additionally by Fourier transform mid-infrared spectroscopy and scanning electron microscopy. It was found that the solubility of this sample was 6.5-fold higher than that of bulk hydrochlorothiazide. Full article
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Open AccessArticle Phenolic and Volatile Composition of a Dry Spearmint (Mentha spicata L.) Extract
Molecules 2016, 21(8), 1007; doi:10.3390/molecules21081007
Received: 6 June 2016 / Revised: 25 July 2016 / Accepted: 27 July 2016 / Published: 3 August 2016
Cited by 6 | PDF Full-text (744 KB) | HTML Full-text | XML Full-text
Abstract
The present paper reports a complete mass spectrometric characterization of both the phenolic and volatile fractions of a dried spearmint extract. Phenolic compounds were analysed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MSn) and a total of 66 compounds were tentatively
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The present paper reports a complete mass spectrometric characterization of both the phenolic and volatile fractions of a dried spearmint extract. Phenolic compounds were analysed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MSn) and a total of 66 compounds were tentatively identified, being the widest phenolic characterisation of spearmint to date. The analysis suggests that the extract is composed of rosmarinic acid and its derivatives (230.5 ± 13.5 mg/g) with smaller amounts of salvianolic acids, caffeoylquinic acids, hydroxybenzoic acids, hydroxycinnamic acids, flavones, and flavanones. Head space solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) technique, that was applied to characterize the volatile fraction of spearmint, identified molecules belonging to different chemical classes, such as p-cymene, isopiperitone, and piperitone, dihydroedulan II, menthone, p-cymen-8-ol, and β-linalool. This comprehensive phytochemical analysis can be useful to test the authenticity of this product rich in rosmarinic acid and other phenolics, and when assessing its biological properties. It may also be applied to other plant-derived food extracts and beverages containing a broad range of phytochemical compounds. Full article
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Open AccessArticle In Vivo Release Kinetics and Antibacterial Activity of Novel Polyphenols-Enriched Chewing Gums
Molecules 2016, 21(8), 1008; doi:10.3390/molecules21081008
Received: 8 June 2016 / Revised: 27 July 2016 / Accepted: 29 July 2016 / Published: 2 August 2016
Cited by 2 | PDF Full-text (1303 KB) | HTML Full-text | XML Full-text
Abstract
Chewing gums may be particularly effective means for delivering and maintaining bioactive molecules, included in the gum formulation, able to have an anti-cariogenic effect. The purposes of this study were: to develop novel chewing gums containing quercetin (Qt); to evaluate their release using
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Chewing gums may be particularly effective means for delivering and maintaining bioactive molecules, included in the gum formulation, able to have an anti-cariogenic effect. The purposes of this study were: to develop novel chewing gums containing quercetin (Qt); to evaluate their release using in vivo trial; finally, to test their in vivo antibacterial effect against oral Streptococcus mutans strains. A preliminary study was performed to produce new gums, enriched with the polyphenol quercetin. Then, a first in vivo experimental study was assessed to test the percentages of Qt released in the saliva of young volunteers. Moreover, a second clinical trial was performed to analyze the antibacterial capability of these enriched chewing gums against S. mutans strains after 14 days of daily consumption. The release analysis showed that a more effective release of Qt occurs in the first minutes of chewing, and it does not change saliva pH values. Moreover, Qt included in gums demonstrates an effective antibacterial activity, showing a reduction of the concentration of S. mutans strains in saliva samples, especially after 7 days. Qt included in experimental chewing gums could be efficiently released into the oral cavity and could promote an effective anti-caries concentration in volunteer’s saliva, without changing salivary pH values. Full article
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Open AccessArticle Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells
Molecules 2016, 21(8), 1009; doi:10.3390/molecules21081009
Received: 13 June 2016 / Revised: 19 July 2016 / Accepted: 29 July 2016 / Published: 2 August 2016
Cited by 7 | PDF Full-text (1625 KB) | HTML Full-text | XML Full-text
Abstract
The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin
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The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MSn. The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism. Full article
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Open AccessArticle Synthesis, Biological Profiling and Determination of the Tubulin-Bound Conformation of 12-Aza-Epothilones (Azathilones)
Molecules 2016, 21(8), 1010; doi:10.3390/molecules21081010
Received: 29 June 2016 / Revised: 24 July 2016 / Accepted: 27 July 2016 / Published: 3 August 2016
Cited by 1 | PDF Full-text (2245 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
12-Aza-epothilones (azathilones) incorporating quinoline side chains and bearing different N12-substituents have been synthesized via highly efficient RCM-based macrocyclizations. Quinoline-based azathilones with the side chain N-atom in the meta-position to the C15 atom in the macrocycle are highly potent inhibitors of cancer cell
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12-Aza-epothilones (azathilones) incorporating quinoline side chains and bearing different N12-substituents have been synthesized via highly efficient RCM-based macrocyclizations. Quinoline-based azathilones with the side chain N-atom in the meta-position to the C15 atom in the macrocycle are highly potent inhibitors of cancer cell growth in vitro. In contrast, shifting the quinoline nitrogen to the position para to C15 leads to a ca. 1000-fold loss in potency. Likewise, the desaturation of the C9-C10 bond in the macrocycle to an E double bond produces a substantial reduction in antiproliferative activity. This is in stark contrast to the effect exerted by the same modification in the natural epothilone macrocycle. The conformation of a representative azathilone bound to α/β-tubulin heterodimers was determined based on TR-NOE measurements and a model for the posture of the compound in its binding site on β-tubulin was deduced through a combination of STD measurements and CORCEMA-ST calculations. The tubulin-bound, bioactive conformation of azathilones was found to be overall similar to that of epothilones A and B. Full article
(This article belongs to the Special Issue New Generation of Microtubule-Interacting Anticancer Agents)
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Open AccessArticle Struvite Precipitation as a Means of Recovering Nutrients and Mitigating Ammonia Toxicity in a Two-Stage Anaerobic Digester Treating Protein-Rich Feedstocks
Molecules 2016, 21(8), 1011; doi:10.3390/molecules21081011
Received: 2 July 2016 / Revised: 26 July 2016 / Accepted: 28 July 2016 / Published: 3 August 2016
Cited by 1 | PDF Full-text (1172 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Accumulation of ammonia, measured as total ammonia nitrogen (TAN), a product of protein decomposition in slaughterhouse wastes, inhibits the anaerobic digestion process, reducing digester productivity and leading to failure. Struvite precipitation (SP) is an effective means to remove TAN and enhance the buffering
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Accumulation of ammonia, measured as total ammonia nitrogen (TAN), a product of protein decomposition in slaughterhouse wastes, inhibits the anaerobic digestion process, reducing digester productivity and leading to failure. Struvite precipitation (SP) is an effective means to remove TAN and enhance the buffering of substrates. Different Mg and P sources were evaluated as reactants in SP in acidogenic digester effluents to reduce its TAN levels. In order to measure impact of TAN removal, a standard biochemical methane potential (BMP) test was conducted to measure methane yield from treatments that had the highest TAN reductions. SP results showed 6 of 9 reagent combinations resulted in greater than 70% TAN removal. The BMP results indicated that SP treatment by adding Mg(OH)2 and H3PO4 resulted in 57.6% nitrogen recovery and 41.7% increase in methane yield relative to the substrate without SP. SP is an effective technology to improve nutrient recovery and methane production from the anaerobic digestion of protein-rich feedstocks. Full article
(This article belongs to the Special Issue Green Biorefinery)
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Open AccessArticle Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors
Molecules 2016, 21(8), 1012; doi:10.3390/molecules21081012
Received: 2 June 2016 / Revised: 12 July 2016 / Accepted: 29 July 2016 / Published: 3 August 2016
Cited by 3 | PDF Full-text (3933 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR) kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against
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A series of novel benzohydrazide derivatives containing dihydropyrazoles have been synthesized as potential epidermal growth factor receptor (EGFR) kinase inhibitors and their biological activities as potential antiproliferative agents have been evaluated. Among these compounds, compound H20 exhibited the most potent antiproliferative activity against four cancer cell line variants (A549, MCF-7, HeLa, HepG2) with IC50 values of 0.46, 0.29, 0.15 and 0.21 μM respectively, which showed the most potent EGFR inhibition activities (IC50 = 0.08 μM for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity and activity relationship (SAR) of these benzohydrazide derivatives. These results suggested that compound H20 may be a promising anticancer agent. Full article
(This article belongs to the Special Issue Kinase Inhibitor Chemistry)
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Open AccessArticle Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines
Molecules 2016, 21(8), 1013; doi:10.3390/molecules21081013
Received: 26 May 2016 / Revised: 20 July 2016 / Accepted: 27 July 2016 / Published: 4 August 2016
Cited by 2 | PDF Full-text (1846 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite prevention and treatment options, breast cancer (BC) has become one of the most important issues in the present day. Therefore, the need for more specific and efficient compounds remains paramount. We evaluated four previously isolated aryltetralin lignans: 5′-demethoxy-β-peltatin-A-methylether (1), acetylpodophyllotoxin
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Despite prevention and treatment options, breast cancer (BC) has become one of the most important issues in the present day. Therefore, the need for more specific and efficient compounds remains paramount. We evaluated four previously isolated aryltetralin lignans: 5′-demethoxy-β-peltatin-A-methylether (1), acetylpodophyllotoxin (2), 5′-demethoxydeoxypodophyllotoxin (3), and 7′,8′-dehydroacetylpodophyllotoxin (4) for cytotoxicity, clonogenicity, and selectivity against three BC cell lines: MCF-7, MDA-MB-231, and BT-549, as well as the non-tumorigenic mammary epithelial cell line MCF-10A. Cytotoxicity was evaluated after 72 h of treatment, and clonogenicity was determined at 72 h post-treatment; experiments were performed using the sulforhodamine B staining assay. Selective-index (SI) was calculated by comparing pure compound IC50 values in MCF-10A cell line against the IC50 of the same compound in cancer cell lines. Structural similarities among lignans and controls (podophyllotoxin and etoposide) were analyzed using the Tanimoto coefficient (Tc). Lignans were cytotoxic against all tested cell lines (0.011–7.22 µM) and clonogenicity testing showed a dose-dependent cytocidality for all lignans (≥0.08 µg/mL); compounds 2 and 3 were more potent (14.1 and 7.6 respectively) than etoposide in BT-549 cell line, while compound 2 displayed selectivity (SI = 28.17) in BT-549 cell line. Tc values of lignans suggested a greater similarity with podophyllotoxin structure. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle The Herbal Medicine KIOM-MA128 Inhibits the Antigen/IgE-Mediated Allergic Response in Vitro and in Vivo
Molecules 2016, 21(8), 1015; doi:10.3390/molecules21081015
Received: 6 July 2016 / Revised: 29 July 2016 / Accepted: 2 August 2016 / Published: 4 August 2016
Cited by 3 | PDF Full-text (2213 KB) | HTML Full-text | XML Full-text
Abstract
KIOM-MA128, a novel herbal medicine, has been reported to exert some beneficial effects on various biological events, such as atopic dermatitis, inflammation and cancer. The aim of this study is to investigate how KIOM-MA128 regulates the allergic response. We measured the activity of
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KIOM-MA128, a novel herbal medicine, has been reported to exert some beneficial effects on various biological events, such as atopic dermatitis, inflammation and cancer. The aim of this study is to investigate how KIOM-MA128 regulates the allergic response. We measured the activity of β-hexosaminidase and the levels of allergic mediators in the conditioned media of antigen/IgE (Ag/IgE)-activated RBL-2H3 mast cells. We examined the levels of proteins associated with both the FcεRI and arachidonate cascades. Finally, we established the passive cutaneous anaphylaxis (PCA) model in mice to confirm the anti-allergic effects of KIOM-MA128 in vivo. KIOM-MA128 dose-dependently inhibited degranulation and the production of the allergic mediators described above, with no significant cytotoxicity. In the arachidonate cascade, KIOM-MA128 significantly reduced both cytosolic phospholipase A2 (cPLA2) phosphorylation and cyclooxygenase-2 (COX-2) expression. Moreover, in the FcεRI cascade, KIOM-MA128 not only inhibited activation of LYN, FYN and SYK, known as the rate-limiting proteins of the FcεRI cascade, but also suppressed the phosphorylation of ERK, p38 and JNK, which is related to cytokine expression. Finally, 50 to 100 mg/kg KIOM-MA128 significantly attenuated the Ag/IgE-induced PCA reaction in mice. These findings provide novel information and improve our understanding of the anti-allergic effects of KIOM-MA128 on allergic diseases. Full article
(This article belongs to the Special Issue Natural Products and Inflammation)
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Open AccessArticle Preparative Separation of Phenolic Compounds from Chimonanthus praecox Flowers by High-Speed Counter-Current Chromatography Using a Stepwise Elution Mode
Molecules 2016, 21(8), 1016; doi:10.3390/molecules21081016
Received: 29 June 2016 / Revised: 25 July 2016 / Accepted: 31 July 2016 / Published: 4 August 2016
Cited by 4 | PDF Full-text (2905 KB) | HTML Full-text | XML Full-text
Abstract
High-speed counter-current chromatography (HSCCC) has been successfully used for the separation of eight compounds from Chimonanthus praecox flowers. Firstly, the crude extract of Chimonanthus praecox flowers was dissolved in a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–H2O (5:5:3:7, v/v)
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High-speed counter-current chromatography (HSCCC) has been successfully used for the separation of eight compounds from Chimonanthus praecox flowers. Firstly, the crude extract of Chimonanthus praecox flowers was dissolved in a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–H2O (5:5:3:7, v/v) and divided into two parts: the upper phase (part I) and the lower phase (part II). Then, HSCCC was applied to separate the phenolic acids from part I and part II, respectively. Considering the broad polarity range of target compounds in part I, a stepwise elution mode was established. Two optimal solvent systems of petroleum ether–ethyl acetate–methanol–H2O–formic acid (FA) (5:5:3:7:0.02, 5:5:4.3:5.7:0.02, v/v) were employed in this separation. Five phenylpropanoids and two flavonoids were successfully separated from 280 mg of part I, including 8.7 mg of 3,4-dihydroxy benzoic acid (a, 95.3% purity), 10.9 mg of protocatechualdehyde (b, 96.8% purity), 11.3 mg of p-coumaric acid (c, 98.9% purity), 12.2 mg of p-hydroxybenzaldehyde (d, 95.9% purity), 24.7 mg of quercetin (e, 97.3% purity), 33.8 mg of kaempferol (f, 96.8% purity), and 24.6 mg of 4-hydroxylcinnamic aldehyde (g, 98.0% purity). From 300 mg of part II, 65.7 mg of rutin (h, 98.2% purity), 7.5 mg of 3,4-dihydroxy benzoic acid (a, 77.4% purity), and 4.7 mg of protocatechualdehyde (b, 81.6% purity) were obtained using the solvent system EtOAc–n-butanol (n-BuOH)–FA–H2O (4:1:0.5:5, v/v). The structures of the eight pure compounds were confirmed by electrospray ionization-mass spectrometry (ESI-MS), 1H-NMR and 13C-NMR. To the best of our knowledge, compounds ad and f were the first separated and reported from the Chimonanthus praecox flower extract. Full article
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Open AccessArticle Laccase Gene Family in Cerrena sp. HYB07: Sequences, Heterologous Expression and Transcriptional Analysis
Molecules 2016, 21(8), 1017; doi:10.3390/molecules21081017
Received: 2 June 2016 / Revised: 26 July 2016 / Accepted: 26 July 2016 / Published: 4 August 2016
Cited by 2 | PDF Full-text (2664 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Laccases are a class of multi-copper oxidases with industrial potential. In this study, eight laccases (Lac1–8) from Cerrena sp. strain HYB07, a white-rot fungus with high laccase yields, were analyzed. The laccases showed moderate identities to each other as well as with other
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Laccases are a class of multi-copper oxidases with industrial potential. In this study, eight laccases (Lac1–8) from Cerrena sp. strain HYB07, a white-rot fungus with high laccase yields, were analyzed. The laccases showed moderate identities to each other as well as with other fungal laccases and were predicted to have high redox potentials except for Lac6. Selected laccase isozymes were heterologously expressed in the yeast Pichia pastoris, and different enzymatic properties were observed. Transcription of the eight laccase genes was differentially regulated during submerged and solid state fermentation, as shown by quantitative real-time polymerase chain reaction and validated reference genes. During 6-day submerged fermentation, Lac7 and 2 were successively the predominantly expressed laccase gene, accounting for over 95% of all laccase transcripts. Interestingly, accompanying Lac7 downregulation, Lac2 transcription was drastically upregulated on days 3 and 5 to 9958-fold of the level on day 1. Consistent with high mRNA abundance, Lac2 and 7, but not other laccases, were identified in the fermentation broth by LC-MS/MS. In solid state fermentation, less dramatic differences in transcript abundance were observed, and Lac3, 7 and 8 were more highly expressed than other laccase genes. Elucidating the properties and expression profiles of the laccase gene family will facilitate understanding, production and commercialization of the fungal strain and its laccases. Full article
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Open AccessArticle Modulation of Neural Network Activity through Single Cell Ablation: An in Vitro Model of Minimally Invasive Neurosurgery
Molecules 2016, 21(8), 1018; doi:10.3390/molecules21081018
Received: 10 June 2016 / Revised: 25 July 2016 / Accepted: 1 August 2016 / Published: 5 August 2016
Cited by 1 | PDF Full-text (5073 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The technological advancement of optical approaches, and the growth of their applications in neuroscience, has allowed investigations of the physio-pathology of neural networks at a single cell level. Therefore, better understanding the role of single neurons in the onset and progression of neurodegenerative
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The technological advancement of optical approaches, and the growth of their applications in neuroscience, has allowed investigations of the physio-pathology of neural networks at a single cell level. Therefore, better understanding the role of single neurons in the onset and progression of neurodegenerative conditions has resulted in a strong demand for surgical tools operating with single cell resolution. Optical systems already provide subcellular resolution to monitor and manipulate living tissues, and thus allow understanding the potentiality of surgery actuated at single cell level. In the present work, we report an in vitro experimental model of minimally invasive surgery applied on neuronal cultures expressing a genetically encoded calcium sensor. The experimental protocol entails the continuous monitoring of the network activity before and after the ablation of a single neuron, to provide a robust evaluation of the induced changes in the network activity. We report that in subpopulations of about 1000 neurons, even the ablation of a single unit produces a reduction of the overall network activity. The reported protocol represents a simple and cost effective model to study the efficacy of single-cell surgery, and it could represent a test-bed to study surgical procedures circumventing the abrupt and complete tissue removal in pathological conditions. Full article
(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)
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Open AccessArticle Optimization and Biodistribution of [11C]-TKF, An Analog of Tau Protein Imaging Agent [18F]-THK523
Molecules 2016, 21(8), 1019; doi:10.3390/molecules21081019
Received: 27 May 2016 / Revised: 1 August 2016 / Accepted: 3 August 2016 / Published: 5 August 2016
Cited by 1 | PDF Full-text (2589 KB) | HTML Full-text | XML Full-text
Abstract
The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer’s disease (AD) and allow monitoring of disease progression and treatment efficacy. [18F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention
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The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer’s disease (AD) and allow monitoring of disease progression and treatment efficacy. [18F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [11C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [11C]-TKF can be made by reaction precursor with [11C]MeOTf or 11CH3I, but [11C]MeOTf will give us higher labeling yields and specific activity. [11C]-TKF presented better brain uptake in normal mouse than [18F]-THK523 (3.23% ± 1.25% ID·g−1 vs. 2.62% ± 0.39% ID·g−1 at 2 min post-injection). The acute toxicity studies of [11C]-TKF were unremarkable. Full article
(This article belongs to the Special Issue Molecules against Alzheimer)
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Open AccessArticle X-ray Single Crystal Structure, DFT Calculations and Biological Activity of 2-(3-Methyl-5-(pyridin-2’-yl)-1H-pyrazol-1-yl) Ethanol
Molecules 2016, 21(8), 1020; doi:10.3390/molecules21081020
Received: 19 July 2016 / Revised: 31 July 2016 / Accepted: 2 August 2016 / Published: 5 August 2016
PDF Full-text (2874 KB) | HTML Full-text | XML Full-text
Abstract
A pyridylpyrazole bearing a hydroxyethyl substituent group has been synthesized by condensation of (Z)-4-hydroxy-4-(pyridin-2-yl)but-3-en-2-one with 2-hydroxyethylhydrazine. The compound was well characterized and its structure confirmed by single crystal X-ray diffraction. Density functional calculations have been performed using DFT method with 6-31G*
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A pyridylpyrazole bearing a hydroxyethyl substituent group has been synthesized by condensation of (Z)-4-hydroxy-4-(pyridin-2-yl)but-3-en-2-one with 2-hydroxyethylhydrazine. The compound was well characterized and its structure confirmed by single crystal X-ray diffraction. Density functional calculations have been performed using DFT method with 6-31G* basis set. The HOMO-LUMO energy gap, binding energies and electron deformation densities are calculated at the DFT (BLYP, PW91, PWC) level. The electrophilic f(−) and nucleophilic f(+) Fukui functions and also the electrophilic and nucleophilic Parr functions are well adapted to find the electrophile and nucleophile centers in the molecule. The title compound has been tested for its DPPH radical scavenging activity which is involved in aging processes, anti-inflammatory, anticancer and wound healing activity. Compound is also found with a significant antioxidant activity, probably due to the ability to donate a hydrogen atom to the DPPH radical. Full article
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Open AccessArticle Siegesbeckia orientalis Extract Inhibits TGFβ1-Induced Migration and Invasion of Endometrial Cancer Cells
Molecules 2016, 21(8), 1021; doi:10.3390/molecules21081021
Received: 12 July 2016 / Revised: 1 August 2016 / Accepted: 3 August 2016 / Published: 5 August 2016
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Abstract
Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol
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Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE) on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ). The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessCommunication Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice
Molecules 2016, 21(8), 1022; doi:10.3390/molecules21081022
Received: 20 June 2016 / Revised: 21 July 2016 / Accepted: 30 July 2016 / Published: 5 August 2016
Cited by 2 | PDF Full-text (1296 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase
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In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice. Full article
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Open AccessArticle A Simple and Effective Ratiometric Fluorescent Probe for the Selective Detection of Cysteine and Homocysteine in Aqueous Media
Molecules 2016, 21(8), 1023; doi:10.3390/molecules21081023
Received: 18 July 2016 / Revised: 2 August 2016 / Accepted: 2 August 2016 / Published: 5 August 2016
Cited by 5 | PDF Full-text (3420 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Biothiols such as cysteine (Cys) and homocysteine (Hcy) are essential biomolecules participating in molecular and physiological processes in an organism. However, their selective detection remains challenging. In this study, ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (NL) was synthesized as a ratiometric fluorescent probe for the
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Biothiols such as cysteine (Cys) and homocysteine (Hcy) are essential biomolecules participating in molecular and physiological processes in an organism. However, their selective detection remains challenging. In this study, ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (NL) was synthesized as a ratiometric fluorescent probe for the rapid and selective detection of Cys and Hcy over glutathione (GSH) and other amino acids. The fluorescence intensity of the probe in the presence of Cys/Hcy increased about 3-fold at a concentration of 20 equiv. of the probe, compared with that in the absence of these chemicals in aqueous media. The limits of detection of the fluorescent assay were 0.911 μM and 0.828 μM of Cys and Hcy, respectively. 1H-NMR and MS analyses indicated that an excited-state intramolecular proton transfer is the mechanism of fluorescence sensing. This ratiometric probe is structurally simple and highly selective. The results suggest that it has useful applications in analytical chemistry and diagnostics. Full article
(This article belongs to the Special Issue Molecular Imaging Probes)
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Open AccessArticle Variations in Essential Oil Yield, Composition, and Antioxidant Activity of Different Plant Organs from Blumea balsamifera (L.) DC. at Different Growth Times
Molecules 2016, 21(8), 1024; doi:10.3390/molecules21081024
Received: 14 June 2016 / Revised: 28 July 2016 / Accepted: 1 August 2016 / Published: 5 August 2016
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Abstract
Blumea balsamifera, also named Ainaxiang, is widely used as an ancient medicinal herb in tropical and subtropical Asia. It is rich in essential oils. In this work the essential oils of B. balsamifera from different plant organs and in different months were
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Blumea balsamifera, also named Ainaxiang, is widely used as an ancient medicinal herb in tropical and subtropical Asia. It is rich in essential oils. In this work the essential oils of B. balsamifera from different plant organs and in different months were extracted, and then analyzed by gas chromatography-mass spectrometry. The results showed that essential oil yield of young leaves was the highest (0.65 mL/100 g), followed by mature leaves (0.57 mL/100 g), and the oil yield was higher in October (0.47 mL/100 g) than other months. A total of 44 compounds were identified, representing 92.64%–96.71% of the oil. Eighteen common chemical components were found among the six plant organs, representing >80% of the oil constituents. l-borneol was the main ingredient in leaves, and its content was the highest in senescent leaves and in December. In the essential oils of young shoots and young stems, the main component was dimethoxydurene. Antioxidant activity was also determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene bleaching (BCB) assays. The results indicated that the β-carotene bleaching activity was far stronger than the DPPH radical-scavenging capacity, and the young leaves and young shoots showed stronger antioxidant activity. Dimethoxydurene, β-caryophyllene, and α-caryophyllene play a positive role in good antioxidant activity, while β-eudesmol, phytol, and tetradecanal play a negative role. The antioxidant activity revealed in this study might help in developing this promising bioresource for use in the medicinal and cosmetic industries. Full article
(This article belongs to the collection Herbal Medicine Research)
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Open AccessArticle Porphyrin Dye-Sensitized Zinc Oxide Aggregated Anodes for Use in Solar Cells
Molecules 2016, 21(8), 1025; doi:10.3390/molecules21081025
Received: 17 June 2016 / Revised: 20 July 2016 / Accepted: 3 August 2016 / Published: 5 August 2016
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Abstract
Porphyrin YD2-o-C8-based dyes were employed to sensitize room-temperature (RT) chemical-assembled ZnO aggregated anodes for use in dye-sensitized solar cells (DSSCs). To reduce the acidity of the YD2-o-C8 dye solution, the proton in the carboxyl group of a porphyrin dye was replaced with tetrabuthyl
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Porphyrin YD2-o-C8-based dyes were employed to sensitize room-temperature (RT) chemical-assembled ZnO aggregated anodes for use in dye-sensitized solar cells (DSSCs). To reduce the acidity of the YD2-o-C8 dye solution, the proton in the carboxyl group of a porphyrin dye was replaced with tetrabuthyl ammonium (TBA+) in this work. The short-circuit current density (Jsc) of the YD2-o-C8-TBA-sensitized ZnO DSSCs is higher than that of the YD2-o-C8-sensitized cells, resulting in the improvement of the efficiency of the YD2-o-C8-based ZnO DSSCs. With an appropriate incorporation of chenodeoxycholic acid (CDCA) as coadsorbate, the Jsc and efficiency of the YD2-o-C8-TBA-sensitized ZnO DSSC are enhanced due to the improvement of the incident-photon-to-current efficiency (IPCE) values in the wavelength range of 400–450 nm. Moreover, a considerable increase in Jsc is achieved by the addition of a light scattering layer in the YD2-o-C8-TBA-sensitized ZnO photoanodes. Significant IPCE enhancement in the range 475–600 nm is not attainable by tuning the YD2-o-C8-TBA sensitization processes for the anodes without light scattering layers. Using the RT chemical-assembled ZnO aggregated anode with a light scattering layer, an efficiency of 3.43% was achieved in the YD2-o-C8-TBA-sensitized ZnO DSSC. Full article
(This article belongs to the Special Issue Dye‐Sensitized Solar Cells)
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Open AccessArticle Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats
Molecules 2016, 21(8), 1026; doi:10.3390/molecules21081026
Received: 23 June 2016 / Revised: 20 July 2016 / Accepted: 28 July 2016 / Published: 9 August 2016
Cited by 3 | PDF Full-text (3744 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat
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Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese–diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessCommunication Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists
Molecules 2016, 21(8), 1027; doi:10.3390/molecules21081027
Received: 31 May 2016 / Revised: 31 July 2016 / Accepted: 2 August 2016 / Published: 6 August 2016
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Abstract
Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the
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Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl d-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic δ-oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson’s disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessArticle Glutamine Synthetase Drugability beyond Its Active Site: Exploring Oligomerization Interfaces and Pockets
Molecules 2016, 21(8), 1028; doi:10.3390/molecules21081028
Received: 8 June 2016 / Revised: 1 August 2016 / Accepted: 4 August 2016 / Published: 8 August 2016
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Abstract
Background: Glutamine synthetase (GS) is a crucial enzyme to the nitrogen cycle with great commercial and pharmaceutical value. Current inhibitors target the active site, affecting GS activity indiscriminately in all organisms. As the active site is located at the interface between two
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Background: Glutamine synthetase (GS) is a crucial enzyme to the nitrogen cycle with great commercial and pharmaceutical value. Current inhibitors target the active site, affecting GS activity indiscriminately in all organisms. As the active site is located at the interface between two monomers, the protein-protein interface (PPI) of GSs gains a new role, by providing new targets for enzyme inhibition. Exploring GSs PPI could allow for the development of inhibitors selective for specific organisms. Here we map the PPI of three GSs—human (hsGS), maize (zmGS) and Mycobacterium tuberculosis (mtGS)—and unravel new drugable pockets. Methods: The PPI binding free energy coming from key residues on three GSs from different organisms were mapped by computational alanine scan mutagenesis, applying a multiple dielectric constant MM-PBSA methodology. The most relevant residues for binding are referred as hot-spots. Drugable pockets on GS were detected with the Fpocket software. Results and Conclusions: A total of 23, 19 and 30 hot-spots were identified on hsGS, zmGS and mtGS PPI. Even possessing differences in the hot-spots, hsGS and zmGS PPI are overall very similar. On the other hand, mtGS PPI differs greatly from hsGS and zmGS PPI. A novel drugable pocket was detected on the mtGS PPI. It seems particularly promising for the development of selective anti-tuberculosis drugs given its location on a PPI region that is highly populated with hot-spots and is completely different from the hsGS and zmGS PPIs. Drugs targeting this pockets should be inactive on eukaryotic GS II enzymes. Full article
(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)
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Open AccessArticle The Complete Chloroplast Genome Sequence of the Medicinal Plant Swertia mussotii Using the PacBio RS II Platform
Molecules 2016, 21(8), 1029; doi:10.3390/molecules21081029
Received: 21 June 2016 / Revised: 21 July 2016 / Accepted: 4 August 2016 / Published: 9 August 2016
Cited by 4 | PDF Full-text (2061 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Swertia mussotii is an important medicinal plant that has great economic and medicinal value and is found on the Qinghai Tibetan Plateau. The complete chloroplast (cp) genome of S. mussotii is 153,431 bp in size, with a pair of inverted repeat (IR) regions
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Swertia mussotii is an important medicinal plant that has great economic and medicinal value and is found on the Qinghai Tibetan Plateau. The complete chloroplast (cp) genome of S. mussotii is 153,431 bp in size, with a pair of inverted repeat (IR) regions of 25,761 bp each that separate an large single-copy (LSC) region of 83,567 bp and an a small single-copy (SSC) region of 18,342 bp. The S. mussotii cp genome encodes 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The identity, number, and GC content of S. mussotii cp genes were similar to those in the genomes of other Gentianales species. Via analysis of the repeat structure, 11 forward repeats, eight palindromic repeats, and one reverse repeat were detected in the S. mussotii cp genome. There are 45 SSRs in the S. mussotii cp genome, the majority of which are mononucleotides found in all other Gentianales species. An entire cp genome comparison study of S. mussotii and two other species in Gentianaceae was conducted. The complete cp genome sequence provides intragenic information for the cp genetic engineering of this medicinal plant. Full article
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Open AccessArticle TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds
Molecules 2016, 21(8), 1030; doi:10.3390/molecules21081030
Received: 30 June 2016 / Revised: 27 July 2016 / Accepted: 3 August 2016 / Published: 10 August 2016
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Abstract
Cyanation reactions of carbonyl compounds with methyl cyanoformate or acetyl cyanide catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were examined. Using methyl cyanoformate, the corresponding cyanohydrin carbonates were readily obtained in high yield for aromatic and aliphatic aldehydes and ketones. Similar results
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Cyanation reactions of carbonyl compounds with methyl cyanoformate or acetyl cyanide catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were examined. Using methyl cyanoformate, the corresponding cyanohydrin carbonates were readily obtained in high yield for aromatic and aliphatic aldehydes and ketones. Similar results were obtained when acetyl cyanide was used as the cyanide source. The polymer-supported catalyst, PS-TBD, also acted as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal activity loss. Full article
(This article belongs to the collection Recent Advances in Organocatalysis)
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Open AccessArticle New Sesquiterpenenoids from Ainsliaea yunnanensis
Molecules 2016, 21(8), 1031; doi:10.3390/molecules21081031
Received: 22 June 2016 / Revised: 2 August 2016 / Accepted: 3 August 2016 / Published: 8 August 2016
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Abstract
Investigation of the ethanol extract of the whole plant of Ainsliaea yunnanensis led to the isolation of four new dimeric sesquiterpene lactones, ainsliadimer F–I (14), together with seven known dimeric sesquiterpene lactones (511) and ten
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Investigation of the ethanol extract of the whole plant of Ainsliaea yunnanensis led to the isolation of four new dimeric sesquiterpene lactones, ainsliadimer F–I (14), together with seven known dimeric sesquiterpene lactones (511) and ten sesquiterpenes (1221). Their structures were elucidated by spectroscopic methods. The relative stereochemistry of ainsliadimer F was further confirmed by single crystal X-ray diffraction analysis. Compounds 121 were tested for the inhibition of nuclear factor kappa B (NF-κB) in the 293-NF-κB-luciferase reporter cell line induced by lipopolysaccharide (LPS), and Compounds 5, 18, 20 and 21 were further tested for the production of TNF-α, IL-1β, IL-6 and IL-10 in RAW 264.7 macrophages induced by LPS. Compounds 5, 18, 20 and 21 exhibited significant activity in anti-inflammatory activity assays. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway
Molecules 2016, 21(8), 1033; doi:10.3390/molecules21081033
Received: 14 July 2016 / Revised: 3 August 2016 / Accepted: 5 August 2016 / Published: 9 August 2016
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Abstract
Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL), one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor
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Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL), one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2)-regulated genes such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone1) (NQO1). However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and improved the activities of superoxide dismutase (SOD) and catalase (CAT), resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. Full article
(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)
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Open AccessArticle Phytoestrogen Metabolism by Adult Human Gut Microbiota
Molecules 2016, 21(8), 1034; doi:10.3390/molecules21081034
Received: 3 March 2016 / Revised: 22 July 2016 / Accepted: 4 August 2016 / Published: 9 August 2016
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Abstract
Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and
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Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. Full article
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Open AccessArticle Synthesis and Structure-Activity Relationship of Some New Thiophene-Based Heterocycles as Potential Antimicrobial Agents
Molecules 2016, 21(8), 1036; doi:10.3390/molecules21081036
Received: 28 June 2016 / Revised: 23 July 2016 / Accepted: 4 August 2016 / Published: 9 August 2016
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Abstract
Several new pyrazole, pyridine, [1,2,4]triazolo[1,5-α]pyrimidine, benzimidazo[1,2-a]pyrimidine and 1,2,4-triazolo[3,4-c][1,2,4]triazine derivatives incorporating a thiophene moiety were synthesized from (E)-ethyl 5-(3-(dimethylamino)acryloyl)-4-phenyl-2-(phenylamino)thiophene-3-carboxylate (1). The structures of the newly synthesized compounds were confirmed by IR, 1H-, 13C-NMR, mass
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Several new pyrazole, pyridine, [1,2,4]triazolo[1,5-α]pyrimidine, benzimidazo[1,2-a]pyrimidine and 1,2,4-triazolo[3,4-c][1,2,4]triazine derivatives incorporating a thiophene moiety were synthesized from (E)-ethyl 5-(3-(dimethylamino)acryloyl)-4-phenyl-2-(phenylamino)thiophene-3-carboxylate (1). The structures of the newly synthesized compounds were confirmed by IR, 1H-, 13C-NMR, mass spectral data and elemental analysis. The antibacterial and antifungal activities of all the synthesized compounds were evaluated. The results indicated that compounds 9, 12, and 19 were found to be more potent than the standard drug Amphotericin B against Aspergillus fumigates. Additionally, compound 12 exhibited higher activity than the standard drug Amphotericin B against Syncephalastrum racemosum. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Predicting Protein-Protein Interactions Using BiGGER: Case Studies
Molecules 2016, 21(8), 1037; doi:10.3390/molecules21081037
Received: 10 June 2016 / Revised: 3 August 2016 / Accepted: 4 August 2016 / Published: 9 August 2016
Cited by 4 | PDF Full-text (3467 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The importance of understanding interactomes makes preeminent the study of protein interactions and protein complexes. Traditionally, protein interactions have been elucidated by experimental methods or, with lower impact, by simulation with protein docking algorithms. This article describes features and applications of the BiGGER
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The importance of understanding interactomes makes preeminent the study of protein interactions and protein complexes. Traditionally, protein interactions have been elucidated by experimental methods or, with lower impact, by simulation with protein docking algorithms. This article describes features and applications of the BiGGER docking algorithm, which stands at the interface of these two approaches. BiGGER is a user-friendly docking algorithm that was specifically designed to incorporate experimental data at different stages of the simulation, to either guide the search for correct structures or help evaluate the results, in order to combine the reliability of hard data with the convenience of simulations. Herein, the applications of BiGGER are described by illustrative applications divided in three Case Studies: (Case Study A) in which no specific contact data is available; (Case Study B) when different experimental data (e.g., site-directed mutagenesis, properties of the complex, NMR chemical shift perturbation mapping, electron tunneling) on one of the partners is available; and (Case Study C) when experimental data are available for both interacting surfaces, which are used during the search and/or evaluation stage of the docking. This algorithm has been extensively used, evidencing its usefulness in a wide range of different biological research fields. Full article
(This article belongs to the collection Molecular Docking)
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Open AccessArticle Chemo-Enzymatic Synthesis of Oligoglycerol Derivatives
Molecules 2016, 21(8), 1038; doi:10.3390/molecules21081038
Received: 20 July 2016 / Revised: 4 August 2016 / Accepted: 5 August 2016 / Published: 9 August 2016
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Abstract
A cleaner and greener method has been developed and used to synthesize 14 different functionalized oligomer derivatives of glycerol in moderate 29%–39% yields over three steps. After successive regioselective enzymatic acylation of the primary hydroxyl groups, etherification or esterification of the secondary hydroxyl
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A cleaner and greener method has been developed and used to synthesize 14 different functionalized oligomer derivatives of glycerol in moderate 29%–39% yields over three steps. After successive regioselective enzymatic acylation of the primary hydroxyl groups, etherification or esterification of the secondary hydroxyl groups and chemoselective enzymatic saponification, the target compounds can efficiently be used as versatile building blocks in organic and supramolecular chemistry. Full article
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Open AccessArticle Insecticidal Properties of a Highly Potent Wax Isolated from Dolichandra cynanchoides Cham
Molecules 2016, 21(8), 1039; doi:10.3390/molecules21081039
Received: 7 July 2016 / Revised: 1 August 2016 / Accepted: 4 August 2016 / Published: 11 August 2016
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Abstract
Bioassay-guided fractionation of an ethanolic extract of the aerial parts of Dolichandra cynanchoides Cham. (Bignoniaceae) led to the isolation of a natural wax with anti-insect activity against Spodoptera frugiperda (Noctuidae) and Epilachna paenulata (Coleptera). The compound was identified spectroscopically as an ester of
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Bioassay-guided fractionation of an ethanolic extract of the aerial parts of Dolichandra cynanchoides Cham. (Bignoniaceae) led to the isolation of a natural wax with anti-insect activity against Spodoptera frugiperda (Noctuidae) and Epilachna paenulata (Coleptera). The compound was identified spectroscopically as an ester of a C27 fatty acid and a C25 alcohol, pentacosyl heptacosanoate (1). The effective doses of 1 for 50% feeding inhibition (ED50) of S. frugiperda and E. paenulata were 0.82 and 8.53 µg/cm2, respectively, in a choice test, while azadirachtin showed ED50 of 0.10 and 0.59 µg/cm2, respectively. In a no-choice test, both insects refused to feed on leaves treated with 1 at doses of 0.1 µg/cm2 or greater inhibiting larval growth and dramatically reducing survival. The lethal doses 50 (LD50) of 1 were 0.39 and 0.68 µg/cm2 for S. frugiperda and E. paenulata, respectively. These results indicate that 1 has potential for development as botanical insecticides. Similar esters might be obtainable in large quantities as many edible crops produce wax esters that are discarded during food processing. Research on these materials could lead to the detection of similar waxes with insecticidal activity. Full article
(This article belongs to the Section Natural Products)
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Open AccessCommunication Polyamine Metabolites Profiling for Characterization of Lung and Liver Cancer Using an LC-Tandem MS Method with Multiple Statistical Data Mining Strategies: Discovering Potential Cancer Biomarkers in Human Plasma and Urine
Molecules 2016, 21(8), 1040; doi:10.3390/molecules21081040
Received: 8 July 2016 / Revised: 23 July 2016 / Accepted: 2 August 2016 / Published: 10 August 2016
PDF Full-text (4177 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography—tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary
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Polyamines, one of the most important kind of biomarkers in cancer research, were investigated in order to characterize different cancer types. An integrative approach which combined ultra-high performance liquid chromatography—tandem mass spectrometry detection and multiple statistical data processing strategies including outlier elimination, binary logistic regression analysis and cluster analysis had been developed to discover the characteristic biomarkers of lung and liver cancer. The concentrations of 14 polyamine metabolites in biosamples from lung (n = 50) and liver cancer patients (n = 50) were detected by a validated UHPLC-MS/MS method. Then the concentrations were converted into independent variables to characterize patients of lung and liver cancer by binary logic regression analysis. Significant independent variables were regarded as the potential biomarkers. Cluster analysis was engaged for further verifying. As a result, two values was discovered to identify lung and liver cancer, which were the product of the plasma concentration of putrescine and spermidine; and the ratio of the urine concentration of S-adenosyl-l-methionine and N-acetylspermidine. Results indicated that the established advanced method could be successfully applied to characterize lung and liver cancer, and may also enable a new way of discovering cancer biomarkers and characterizing other types of cancer. Full article
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Open AccessArticle Synthesis and Characterization of Process-Related Impurities of Antidiabetic Drug Linagliptin
Molecules 2016, 21(8), 1041; doi:10.3390/molecules21081041
Received: 22 June 2016 / Revised: 3 August 2016 / Accepted: 5 August 2016 / Published: 9 August 2016
Cited by 2 | PDF Full-text (1927 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Linagliptin, a xanthine derivative, is a highly potent, selective, long-acting and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. During the process development of linagliptin, five new process-related impurities were detected by high performance liquid chromatography (HPLC). All these impurities
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Linagliptin, a xanthine derivative, is a highly potent, selective, long-acting and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. During the process development of linagliptin, five new process-related impurities were detected by high performance liquid chromatography (HPLC). All these impurities were identified, synthesized, and subsequently characterized by their respective spectral data (MS, HRMS, 1H-NMR, 13C-NMR and IR) as described in this article. The identification of these impurities should be useful for quality control and the validation of the analytical method in the manufacture of linagliptin. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessCommunication Pd@[nBu4][Br] as a Simple Catalytic System for N-Alkylation Reactions with Alcohols
Molecules 2016, 21(8), 1042; doi:10.3390/molecules21081042
Received: 1 July 2016 / Revised: 28 July 2016 / Accepted: 29 July 2016 / Published: 10 August 2016
Cited by 1 | PDF Full-text (5046 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Palladium nanoparticles, simply and briefly generated in commercial and cheap onium salts using supercritical carbon dioxide, have been found to be an effective catalytic system for additive free N-alkylation reaction using alcohols via cascade oxidation/condensation/reduction steps. Full article
(This article belongs to the Special Issue Cascade Catalysis)
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Open AccessArticle A Versatile Axle for the Construction of Disassemblage Rotaxanes
Molecules 2016, 21(8), 1043; doi:10.3390/molecules21081043
Received: 30 June 2016 / Revised: 2 August 2016 / Accepted: 4 August 2016 / Published: 10 August 2016
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Abstract
Rotaxanes are unique mechanical devices that hold great promise as sensors. We report on two new rotaxanes that contain an acid or base sensitive trigger and readily disassemble in a wide range of environments. Disassemblage was observed under TLC and 1H-NMR analysis.
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Rotaxanes are unique mechanical devices that hold great promise as sensors. We report on two new rotaxanes that contain an acid or base sensitive trigger and readily disassemble in a wide range of environments. Disassemblage was observed under TLC and 1H-NMR analysis. The axle is highly charged, which enhances solubility in aqueous environments, and can be readily derivatized with sensor components. The trigger was swapped in a one-pot method, which is promising for the rapid production of a series of sensors. Full article
(This article belongs to the Special Issue Host-Guest Chemistry)
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Open AccessArticle Catalytic Oxidation of Phenol and 2,4-Dichlorophenol by Using Horseradish Peroxidase Immobilized on Graphene Oxide/Fe3O4
Molecules 2016, 21(8), 1044; doi:10.3390/molecules21081044
Received: 12 April 2016 / Revised: 30 July 2016 / Accepted: 3 August 2016 / Published: 10 August 2016
Cited by 4 | PDF Full-text (1956 KB) | HTML Full-text | XML Full-text
Abstract
Graphene oxide/Fe3O4 (GO/Fe3O4) nanoparticles were synthesized by an ultrasonic-assisted reverse co-precipitation method, and then horseradish peroxidase (HRP) was covalently immobilized onto GO/Fe3O4 with 1-ethyl-3-(3-dimethyaminopropyl)carbodiimide (EDC) as a cross-linking agent. In order to enhance
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Graphene oxide/Fe3O4 (GO/Fe3O4) nanoparticles were synthesized by an ultrasonic-assisted reverse co-precipitation method, and then horseradish peroxidase (HRP) was covalently immobilized onto GO/Fe3O4 with 1-ethyl-3-(3-dimethyaminopropyl)carbodiimide (EDC) as a cross-linking agent. In order to enhance the phenol removal efficiency and prevent the inactivation of the enzyme, the polyethylene glycol with highly hydrophilicity was added in this reaction, because the adsorption capacity for the polymer by degradation was stronger than the HRP. The results showed that the immobilized enzyme removed over 95% of phenol from aqueous solution. The catalytic condition was extensively optimized among the range of pH, mass ratio of PEG/phenol as well as initial concentration of immobilized enzyme and H2O2. The HRP immobilized on GO/Fe3O4 composite could be easily separated under a magnetic field from the reaction solution and reused. Full article
(This article belongs to the Special Issue Enzyme Immobilization 2016)
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Open AccessCommunication In Vitro Antileishmanial Activity of Sterols from Trametes versicolor (Bres. Rivarden)
Molecules 2016, 21(8), 1045; doi:10.3390/molecules21081045
Received: 22 June 2016 / Revised: 1 August 2016 / Accepted: 5 August 2016 / Published: 10 August 2016
Cited by 2 | PDF Full-text (387 KB) | HTML Full-text | XML Full-text
Abstract
Two ergostanes, 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol (1) and 5α-ergost-7,22-dien-3β-ol (2), and a lanostane, 3β-hydroxylanostan-8,24-diene-21-oic acid (trametenolic acid) (3), were isolated from an n-hexane extract prepared from the fruiting body of Trametes versicolor (Bres. Rivarden). The activity of
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Two ergostanes, 5α,8α-epidioxy-22E-ergosta-6,22-dien-3β-ol (1) and 5α-ergost-7,22-dien-3β-ol (2), and a lanostane, 3β-hydroxylanostan-8,24-diene-21-oic acid (trametenolic acid) (3), were isolated from an n-hexane extract prepared from the fruiting body of Trametes versicolor (Bres. Rivarden). The activity of the isolated sterols was evaluated against promastigotes and amastigotes of Leishmania amazonensis Lainson and Shaw, 1972. The lanostane, compound (3), showed the best inhibitory response (IC50 promastigotes 2.9 ± 0.1 μM and IC50 amastigotes 1.6 ± 0.1 μM). This effect was 25-fold higher compared with its cytotoxic effect on peritoneal macrophages from BALB/c mice. Therefore, trametenolic acid could be regarded as a promising lead for the synthesis of compounds with antileishmanial activity. Full article
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Open AccessArticle Anti-Inflammatory Effects of 6,8-Diprenyl-7,4′-dihydroxyflavanone from Sophora tonkinensis on Lipopolysaccharide-Stimulated RAW 264.7 Cells
Molecules 2016, 21(8), 1049; doi:10.3390/molecules21081049
Received: 13 May 2016 / Revised: 5 August 2016 / Accepted: 8 August 2016 / Published: 11 August 2016
Cited by 2 | PDF Full-text (2539 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
The anti-inflammatory effects and molecular mechanism of 6,8-diprenyl-7,4′-dihydroxyflavanone (DDF), one of the flavanones found in Sophora tonkinensis, were assessed in vitro through macrophage-mediated inflammation in the present study. The anti-inflammatory effects of DDF were not previously reported. DDF inhibited the production of
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The anti-inflammatory effects and molecular mechanism of 6,8-diprenyl-7,4′-dihydroxyflavanone (DDF), one of the flavanones found in Sophora tonkinensis, were assessed in vitro through macrophage-mediated inflammation in the present study. The anti-inflammatory effects of DDF were not previously reported. DDF inhibited the production of nitric oxide and the expression of tumor necrosis factor α, interleukin-1β, and interleukin-6. Furthermore, the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases (ERKs) in lipopolysaccharide-stimulated macrophages was suppressed by treatment with DDF. Therefore, DDF demonstrated potentially anti-inflammatory effects via the blockade of NF-κB and ERK activation in macrophages. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Achillea schurii Flowers: Chemical, Antioxidant, and Antimicrobial Investigations
Molecules 2016, 21(8), 1050; doi:10.3390/molecules21081050
Received: 28 June 2016 / Revised: 3 August 2016 / Accepted: 9 August 2016 / Published: 12 August 2016
Cited by 5 | PDF Full-text (1001 KB) | HTML Full-text | XML Full-text
Abstract
This study aims to evaluate the phenolic profile, and antioxidant and antimicrobial activity of Achillea schurii Sch.-Bip., an endemic species from Romania that has not been investigated yet. The chromatographic profile of the phenolic components was obtained using the HPLC-MS method, while
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This study aims to evaluate the phenolic profile, and antioxidant and antimicrobial activity of Achillea schurii Sch.-Bip., an endemic species from Romania that has not been investigated yet. The chromatographic profile of the phenolic components was obtained using the HPLC-MS method, while the total polyphenol, flavonoid, caffeic acid derivative contents were quantified using spectrophotometric methods. The antioxidant activity was evaluated using different methods: DPPH radical scavenging, hemoglobin ascorbate peroxidase activity inhibition (HAPX), inhibition of lipid peroxidation catalyzed by cytochrome c, and direct detection of plant-derived free radicals using electron paramagnetic resonance (EPR). The antimicrobial test was performed using the disk diffusion assay. The phenolic profile has revealed high amounts of isoquercitrin, rutin, luteolin, and apigenin. The A. schurii extract exhibited a good antioxidant capacity, and high phenolic contents (76.93 mg/g polyphenols, 18.61 mg/g flavonoids and 41.48 mg/g caffeic acid derivatives, respectively). The antimicrobial tests reveal a remarkable inhibitory activity against Listeria monocytogenes, Staphylococcus aureus, and Salmonella typhimurium. Considering the above, A. schurii may be deemed to offer good perspectives for pharmaceutical and industrial applications. Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Preparation of Two New Diasteromeric Chiral Stationary Phases Based on (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic Acid and (R)- or (S)-1-(1-Naphthyl)ethylamine and Chiral Tethering Group Effect on the Chiral Recognition
Molecules 2016, 21(8), 1051; doi:10.3390/molecules21081051
Received: 1 July 2016 / Revised: 8 August 2016 / Accepted: 9 August 2016 / Published: 12 August 2016
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Abstract
Two new diastereomeric chiral stationary phases (CSPs) based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral tethering group and a Π-basic chiral unit such as (R)-1-(1-naphthyl)ethylamine (CSP 1) or (S)-1-(1-naphthyl)ethylamine (CSP 2) were prepared. The two CSPs were applied
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Two new diastereomeric chiral stationary phases (CSPs) based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral tethering group and a Π-basic chiral unit such as (R)-1-(1-naphthyl)ethylamine (CSP 1) or (S)-1-(1-naphthyl)ethylamine (CSP 2) were prepared. The two CSPs were applied to the enantiomeric separation of N-(3,5-dinitrobenzoyl)-1-phenylalkylamines and N-(3,5-dinitrobenzoyl)-α-amino acid derivatives using 20% isopropyl alcohol in hexane as a normal mobile phase. To elucidate the effect of the two chiral units on the chiral recognition, the chiral recognition abilities of the two CSPs were compared with each other and with that of a CSP (CSP 3) based on (R)-1-(1-naphthyl)ethylamine. From the chromatographic chiral recognition results, (R)-1-(1-naphthyl)ethylamine and (+)−(18-crown-6)-2,3,11,12-tetracarboxylic acid constituting CSP 1 were concluded to show a cooperative (“matched”) effect on the chiral recognition while (S)-1-(1-naphthyl)ethylamine and (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid constituting CSP 2 were concluded to show an uncooperative (“mismatched”) effect on the chiral recognition. From these results, it was concluded that (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid can be successfully used as a chiral tethering group for the preparation of new CSPs. Full article
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Open AccessArticle In Vitro Inhibition of Human UDP-Glucuronosyl-Transferase (UGT) Isoforms by Astaxanthin, β-Cryptoxanthin, Canthaxanthin, Lutein, and Zeaxanthin: Prediction of in Vivo Dietary Supplement-Drug Interactions
Molecules 2016, 21(8), 1052; doi:10.3390/molecules21081052
Received: 1 July 2016 / Revised: 7 August 2016 / Accepted: 9 August 2016 / Published: 12 August 2016
Cited by 4 | PDF Full-text (701 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despite the widespread use of the five major xanthophylls astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven
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Despite the widespread use of the five major xanthophylls astaxanthin, β-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15) in vitro by LC-MS/MS using specific marker reactions in human liver microsomes (except UGT2B15) or recombinant supersomes (UGT2B15). We also predicted potential dietary supplement-drug interactions for β-cryptoxanthin via UGT1A1 inhibition. We demonstrated that astaxanthin and zeaxanthin showed no apparent inhibition, while the remaining xanthophylls showed only weak inhibitory effects on the seven UGTs. β-Cryptoxanthin mildly inhibited UGT1A1, UGT1A3, and UGT1A4, with IC50 values of 18.8 ± 2.07, 28.3 ± 4.40 and 34.9 ± 5.98 μM, respectively. Canthaxanthin weakly inhibited UGT1A1 and UGT1A3, with IC50 values of 38.5 ± 4.65 and 41.2 ± 3.14 μM, respectively; and lutein inhibited UGT1A1 and UGT1A4, with IC50 values of 45.5 ± 4.01 and 28.7 ± 3.79 μM, respectively. Among the tested xanthophyll-UGT pairs, β-cryptoxanthin showed the strongest competitive inhibition of UGT1A1 (Ki, 12.2 ± 0.985 μM). In addition, we predicted the risk of UGT1A1 inhibition in vivo using the reported maximum plasma concentration after oral administration of β-cryptoxanthin in humans. Our data suggests that these xanthophylls are unlikely to cause dietary supplement-drug interactions mediated by inhibition of the hepatic UGTs. These findings provide useful information for the safe clinical use of the tested xanthophylls. Full article
(This article belongs to the Section Metabolites)
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Open AccessArticle Synthesis and Evaluation of Bicyclo[3.1.0]hexane-Based UDP-Galf Analogues as Inhibitors of the Mycobacterial Galactofuranosyltransferase GlfT2
Molecules 2016, 21(8), 1053; doi:10.3390/molecules21081053
Received: 15 July 2016 / Revised: 5 August 2016 / Accepted: 6 August 2016 / Published: 12 August 2016
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Abstract
UDP-galactofuranose (UDP-Galf) is the donor substrate for both bifunctional galactofuranosyltransferases, GlfT1 and GlfT2, which are involved in the biosynthesis of mycobacterial galactan. In this paper, a group of UDP-Galf mimics were synthesized via reductive amination of a bicyclo[3.1.0]hexane-based amine by
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UDP-galactofuranose (UDP-Galf) is the donor substrate for both bifunctional galactofuranosyltransferases, GlfT1 and GlfT2, which are involved in the biosynthesis of mycobacterial galactan. In this paper, a group of UDP-Galf mimics were synthesized via reductive amination of a bicyclo[3.1.0]hexane-based amine by reacting with aromatic, linear, or uridine-containing aldehydes. These compounds were evaluated against GlfT2 using a coupled spectrophotometric assay, and were shown to be weak inhibitors of the enzyme. Full article
(This article belongs to the Section Organic Synthesis)
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Open AccessArticle Aryloxyalkanoic Acids as Non-Covalent Modifiers of the Allosteric Properties of Hemoglobin
Molecules 2016, 21(8), 1057; doi:10.3390/molecules21081057
Received: 27 June 2016 / Revised: 29 July 2016 / Accepted: 9 August 2016 / Published: 13 August 2016
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Abstract
Hemoglobin (Hb) modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD), specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently
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Hemoglobin (Hb) modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD), specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently being clinically studied for the treatment of SCD. Based on the previously reported non-covalent Hb binding characteristics of substituted aryloxyalkanoic acids that exhibited antisickling properties, we designed, synthesized and evaluated 18 new compounds (KAUS II series) for enhanced antisickling activities. Surprisingly, select test compounds showed no antisickling effects or promoted erythrocyte sickling. Additionally, the compounds showed no significant effect on Hb oxygen affinity (or in some cases, even decreased the affinity for oxygen). The X-ray structure of deoxygenated Hb in complex with a prototype compound, KAUS-23, revealed that the effector bound in the central water cavity of the protein, providing atomic level explanations for the observed functional and biological activities. Although the structural modification did not lead to the anticipated biological effects, the findings provide important direction for designing candidate antisickling agents, as well as a framework for novel Hb allosteric effectors that conversely, decrease the protein affinity for oxygen for potential therapeutic use for hypoxic- and/or ischemic-related diseases. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Synthesis of Natural Homoisoflavonoids Having Either 5,7-Dihydroxy-6-methoxy or 7-Hydroxy-5,6-dimethoxy Groups
Molecules 2016, 21(8), 1058; doi:10.3390/molecules21081058
Received: 14 July 2016 / Revised: 8 August 2016 / Accepted: 9 August 2016 / Published: 13 August 2016
Cited by 2 | PDF Full-text (1142 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Naturally occurring homoisoflavonoids containing either 5,7-dihydroxy-6-methoxy or 7-hydroxy-5,6-dimethoxy groups such as the antiangiogenic homoisoflavanone, cremastranone, were synthesized via three or four linear steps from the known 4-chromenone. This facile synthesis includes chemoselective 1,4-reduction of 4-chromenone and selective deprotection of 3-benzylidene-4-chromanone a containing C7-benzyloxy
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Naturally occurring homoisoflavonoids containing either 5,7-dihydroxy-6-methoxy or 7-hydroxy-5,6-dimethoxy groups such as the antiangiogenic homoisoflavanone, cremastranone, were synthesized via three or four linear steps from the known 4-chromenone. This facile synthesis includes chemoselective 1,4-reduction of 4-chromenone and selective deprotection of 3-benzylidene-4-chromanone a containing C7-benzyloxy group. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle Punica granatum L. Hydrogel for Wound Care Treatment: From Case Study to Phytomedicine Standardization
Molecules 2016, 21(8), 1059; doi:10.3390/molecules21081059
Received: 2 July 2016 / Revised: 7 August 2016 / Accepted: 7 August 2016 / Published: 22 August 2016
Cited by 1 | PDF Full-text (3416 KB) | HTML Full-text | XML Full-text
Abstract
The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the
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The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the effect produced by a magistral formulation of ethanolic extracts of Punica granatum peels on a non-healing chronic ulcer. The complete closure of the chronic ulcer that was initially not responsive to standard medical care was observed. A 2% (w/w) P. granatum peels ethanolic extract hydrogel-based formulation (PGHF) was standardized and subjected to physicochemical studies to establish the quality control parameters using, among others, assessment criteria such as optimum appearance, pH range, viscosity and hydrogel disintegration. The stability and quantitative chromatographic data was assessed in storage for six months under two temperature regimes. An efficient HPLC-DAD method was established distinguishing the biomarkers punicalin and punicalagin simultaneously in a single 8 min run. PGHF presented suitable sensorial and physicochemical performance, showing that punicalagin was not significantly affected by storage (p > 0.05). Formulations containing extracts with not less than 0.49% (w/w) total punicalagin might find good use in wound healing therapy. Full article
(This article belongs to the collection Bioactive Compounds)
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Open AccessArticle Efficient Enzyme-Free Biomimetic Sensors for Natural Phenol Detection
Molecules 2016, 21(8), 1060; doi:10.3390/molecules21081060
Received: 9 July 2016 / Revised: 4 August 2016 / Accepted: 9 August 2016 / Published: 13 August 2016
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Abstract
The development of sensors and biosensors based on copper enzymes and/or copper oxides for phenol sensing is disclosed in this work. The electrochemical properties were studied by cyclic and differential pulse voltammetry using standard solutions of potassium ferrocyanide, phosphate/acetate buffers and representative natural
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The development of sensors and biosensors based on copper enzymes and/or copper oxides for phenol sensing is disclosed in this work. The electrochemical properties were studied by cyclic and differential pulse voltammetry using standard solutions of potassium ferrocyanide, phosphate/acetate buffers and representative natural phenols in a wide pH range (3.0 to 9.0). Among the natural phenols herein investigated, the highest sensitivity was observed for rutin, a powerful antioxidant widespread in functional foods and ubiquitous in the plant kingdom. The calibration curve for rutin performed at optimum pH (7.0) was linear in a broad concentration range, 1 to 120 µM (r = 0.99), showing detection limits of 0.4 µM. The optimized biomimetic sensor was also applied in total phenol determination in natural samples, exhibiting higher stability and sensitivity as well as distinct selectivity for antioxidant compounds. Full article
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Open AccessArticle Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway
Molecules 2016, 21(8), 1061; doi:10.3390/molecules21081061
Received: 19 June 2016 / Revised: 8 August 2016 / Accepted: 10 August 2016 / Published: 22 August 2016
Cited by 7 | PDF Full-text (6451 KB) | HTML Full-text | XML Full-text
Abstract
Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced
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Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications. Full article
(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)
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Open AccessArticle Influence of Cysteine and Tryptophan Substitution on DNA-Binding Activity on Maize α-Hairpinin Antimicrobial Peptide
Molecules 2016, 21(8), 1062; doi:10.3390/molecules21081062
Received: 8 June 2016 / Revised: 29 July 2016 / Accepted: 9 August 2016 / Published: 13 August 2016
Cited by 4 | PDF Full-text (5287 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
For almost four decades, antimicrobial peptides have been studied, and new classes are being discovered. However, for therapeutic use of these molecules, issues related to the mechanism of action must be answered. In this work, the antimicrobial activity of the hairpinin MBP-1 was
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For almost four decades, antimicrobial peptides have been studied, and new classes are being discovered. However, for therapeutic use of these molecules, issues related to the mechanism of action must be answered. In this work, the antimicrobial activity of the hairpinin MBP-1 was studied by the synthesis of two variants, one replacing cysteines and one tryptophan with alanine. Antibacterial activity was abolished in both variants. No membrane disturbance, even in concentrations higher than those required to inhibit the bacteria, was observed in SEM microscopy. The gel retardation assay showed that MBP-1 possesses a higher DNA-binding ability than variants. Finally, molecular modelling showed that the lack of cysteines resulted in structure destabilization and lack of tryptophan resulted in a less flexible peptide, with less solvent assessable surface area, both characteristics that could contribute to absence of activity. In summary, the data here reported add more information about the multiple mechanisms of action of α-hairpinins. Full article
(This article belongs to the Special Issue Peptides as Candidate Chemotherapeutic Drugs)
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Open AccessArticle Physicochemical Changes and Resistant-Starch Content of Extruded Cornstarch with and without Storage at Refrigerator Temperatures
Molecules 2016, 21(8), 1064; doi:10.3390/molecules21081064
Received: 18 June 2016 / Revised: 8 August 2016 / Accepted: 10 August 2016 / Published: 15 August 2016
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Abstract
Effects of extrusion cooking and low-temperature storage on the physicochemical changes and resistant starch (RS) content in cornstarch were evaluated. The cornstarch was conditioned at 20%–40% moisture contents and extruded in the range 90–130 °C and at screw speeds in the range 200–360
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Effects of extrusion cooking and low-temperature storage on the physicochemical changes and resistant starch (RS) content in cornstarch were evaluated. The cornstarch was conditioned at 20%–40% moisture contents and extruded in the range 90–130 °C and at screw speeds in the range 200–360 rpm. The extrudates were stored at 4 °C for 120 h and then at room temperature. The water absorption, solubility index, RS content, viscoelastic, thermal, and microstructural properties of the extrudates were evaluated before and after storage. The extrusion temperature and moisture content significantly affected the physicochemical properties of the extrudates before and after storage. The RS content increased with increasing moisture content and extrusion temperature, and the viscoelastic and thermal properties showed related behaviors. Microscopic analysis showed that extrusion cooking damaged the native starch structure, producing gelatinization and retrogradation and forming RS. The starch containing 35% moisture and extruded at 120 °C and 320 rpm produced the most RS (1.13 g/100 g) after to storage at low temperature. Although the RS formation was low, the results suggest that extrusion cooking could be advantageous for RS production and application in the food industry since it is a pollution less, continuous process requiring only a short residence time. Full article
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Open AccessArticle Biological Activities of the Essential Oil from Erigeron floribundus
Molecules 2016, 21(8), 1065; doi:10.3390/molecules21081065
Received: 12 July 2016 / Revised: 10 August 2016 / Accepted: 11 August 2016 / Published: 13 August 2016
Cited by 5 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study, we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts
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Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study, we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (inhibition zone diameter, IZD of 14 mm, minimum inhibitory concentration, MIC of 512 µg/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 µg/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 µg/mL with the essential oil and 5.6 µg/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 µg/mL, and remarkable ferric reducing antioxidant power (tocopherol-equivalent antioxidant capacity, TEAC = 411.9 μmol·TE/g). Full article
(This article belongs to the Section Natural Products)
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Open AccessArticle Magnetic, Fluorescence and Transition Metal Ion Response Properties of 2,6-Diaminopyridine Modified Silica-Coated Fe3O4 Nanoparticles
Molecules 2016, 21(8), 1066; doi:10.3390/molecules21081066
Received: 23 June 2016 / Revised: 10 August 2016 / Accepted: 10 August 2016 / Published: 15 August 2016
PDF Full-text (4531 KB) | HTML Full-text | XML Full-text
Abstract
Multi-functional nanoparticles possessing magnetic, fluorescence and transition metal ion response properties were prepared and characterized. The particles have a core/shell structure that consists of silica-coated magnetic Fe3O4 and 2,6-diaminopyridine anchored on the silica surface via organic linker molecules. The resultant
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Multi-functional nanoparticles possessing magnetic, fluorescence and transition metal ion response properties were prepared and characterized. The particles have a core/shell structure that consists of silica-coated magnetic Fe3O4 and 2,6-diaminopyridine anchored on the silica surface via organic linker molecules. The resultant nanoparticles were found by transmission electron microscopy to be well-dispersed spherical particles with an average diameter of 10–12 nm. X-ray diffraction analysis suggested the existence of Fe3O4 and silica in/on the particle. Fourier transform infrared spectra revealed that 2,6-diaminopyridine molecules were successfully covalently bonded to the surface of magnetic composite nanoparticles. The prepared particles possessed an emission peak at 364 nm with an excitation wavelength of 307 nm and have a strong reversible response property for some transition metal ions such as Cu2+ and Zn2+. This new material holds considerable promise in selective magneto separation and optical determination applications. Full article
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Open AccessArticle Rapid Isolation and Determination of Flavones in Biological Samples Using Zinc Complexation Coupled with High-Performance Liquid Chromatography
Molecules 2016, 21(8), 1067; doi:10.3390/molecules21081067
Received: 16 June 2016 / Revised: 2 August 2016 / Accepted: 9 August 2016 / Published: 16 August 2016
Cited by 2 | PDF Full-text (1935 KB) | HTML Full-text | XML Full-text
Abstract
Chlorophyll-type contaminants are commonly encountered in the isolation and determination of flavones of plant aerial plant parts. Heme is also a difficult background substance in whole blood analysis. Both chlorophyll and heme are porphyrin type compounds. In this study, a rapid method for
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Chlorophyll-type contaminants are commonly encountered in the isolation and determination of flavones of plant aerial plant parts. Heme is also a difficult background substance in whole blood analysis. Both chlorophyll and heme are porphyrin type compounds. In this study, a rapid method for isolating flavones with 5-hydroxyl or ortho-hydroxyl groups from biological samples was developed based on the different solubilities of porphyrin-metal and flavone-metal complexes. It is important that other background substances, e.g., proteins and lipids, are also removed from flavones without an additional processing. The recoveries of scutellarin, baicalin, baicalein, wogonoside and wogonin, which are the primary constituents of Scutellaria baicalensis (skullcaps) were 99.65% ± 1.02%, 98.98% ± 0.73%, 99.65% ± 0.03%, 97.59% ± 0.09% and 95.19% ± 0.47%, respectively. As a sample pretreatment procedure, this method was coupled to high-performance liquid chromatography (HPLC) with good separation, sensitivity and linearity and was applied to determine the flavone content in different aerial parts of S. baicalensis and in dried blood spot samples. Full article
(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)
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Open AccessArticle N-Alkoxyphenylhydroxynaphthalenecarboxamides and Their Antimycobacterial Activity
Molecules 2016, 21(8), 1068; doi:10.3390/molecules21081068
Received: 27 July 2016 / Revised: 9 August 2016 / Accepted: 12 August 2016 / Published: 16 August 2016
Cited by 6 | PDF Full-text (1120 KB) | HTML Full-text | XML Full-text
Abstract
A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of
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A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. Some of the tested compounds showed antimycobacterial activity comparable with or higher than that of rifampicin. For example, 2-hydroxy-N-(4-propoxyphenyl)-naphthalene-1-carboxamide showed the highest activity (MIC = 12 µM) against M. tuberculosis with insignificant cytotoxicity. N-[3-(But-2-yloxy)phenyl]- and N-[4-(but-2-yloxy)phenyl]-2-hydroxy-naphthalene-1-carboxamide demonstrated high activity against all tested mycobacterial strains and insignificant cytotoxicity. N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides demonstrated rather high effect against M. smegmatis and M. kansasii and strong antiproliferative effect against the human THP-1 cell line. Lipophilicity was found as the main physicochemical parameter influencing the activity. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Structure-activity relationships are discussed. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle Phytochemical Profile and Evaluation of the Biological Activities of Essential Oils Derived from the Greek Aromatic Plant Species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita
Molecules 2016, 21(8), 1069; doi:10.3390/molecules21081069
Received: 18 April 2016 / Revised: 2 August 2016 / Accepted: 10 August 2016 / Published: 16 August 2016
Cited by 4 | PDF Full-text (445 KB) | HTML Full-text | XML Full-text
Abstract
Natural products, known for their medicinal properties since antiquity, are continuously being studied for their biological properties. In the present study, we analyzed the composition of the volatile preparations of essential oils of the Greek plants Ocimum basilicum (sweet basil), Mentha spicata (spearmint),
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Natural products, known for their medicinal properties since antiquity, are continuously being studied for their biological properties. In the present study, we analyzed the composition of the volatile preparations of essential oils of the Greek plants