Molecules

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4 pages, 162 KiB

Open AccessEditorial

Special Issue: “Functional Dendrimers”

by Donald A. Tomalia

Molecules 2016, 21(8), 1035; https://doi.org/10.3390/molecules21081035 - 9 Aug 2016

Cited by 16 | Viewed by 4588

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

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13 pages, 2440 KiB

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

by Shailee V. Tiwari, Julio A. Seijas, M. Pilar Vazquez-Tato, Aniket P. Sarkate, Deepak K. Lokwani and Anna Pratima G. Nikalje

Molecules 2016, 21(8), 894; https://doi.org/10.3390/molecules21080894 - 29 Jul 2016

Cited by 44 | Viewed by 6280

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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24 pages, 2702 KiB

Open AccessArticle

Green Tea Leaves Extract: Microencapsulation, Physicochemical and Storage Stability Study

by James A. Zokti, Badlishah Sham Baharin, Abdulkarim Sabo Mohammed and Faridah Abas

Molecules 2016, 21(8), 940; https://doi.org/10.3390/molecules21080940 - 26 Jul 2016

Cited by 71 | Viewed by 12302

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 [...] Read more.

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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13 pages, 753 KiB

Open AccessArticle

Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives

by Jatinder P. Bassin, Bhavani Anagani, Christopher Benham, Madhu Goyal, Maryam Hashemian and Ute Gerhard

Molecules 2016, 21(8), 967; https://doi.org/10.3390/molecules21080967 - 23 Jul 2016

Cited by 6 | Viewed by 6109

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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9 pages, 1383 KiB

Open AccessArticle

Indole Alkaloids from the Leaves of Nauclea officinalis

by Long Fan, Cheng-Hui Liao, Qiang-Rong Kang, Kai Zheng, Ying-Chun Jiang and Zhen-Dan He

Molecules 2016, 21(8), 968; https://doi.org/10.3390/molecules21080968 - 23 Jul 2016

Cited by 6 | Viewed by 6354

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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19 pages, 5079 KiB

Open AccessArticle

Hybrid Molecules Containing a 7-Chloro-4-aminoquinoline Nucleus and a Substituted 2-Pyrazoline with Antiproliferative and Antifungal Activity

by Alba Montoya, Jairo Quiroga, Rodrigo Abonia, Marcos Derita, Maximiliano Sortino, Alfredo Ornelas, Susana Zacchino and Braulio Insuasty

Molecules 2016, 21(8), 969; https://doi.org/10.3390/molecules21080969 - 27 Jul 2016

Cited by 23 | Viewed by 5834

Abstract

Twenty-four new hybrid analogues (15–38) 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 (15–38) 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 (15–38) were also evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. From the obtained results some structure–activity relationships were outlined. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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7 pages, 559 KiB

Open AccessArticle

Halichoblelide D, a New Elaiophylin Derivative with Potent Cytotoxic Activity from Mangrove-Derived Streptomyces sp. 219807

by Ying Han, Erli Tian, Dongbo Xu, Min Ma, Zixin Deng and Kui Hong

Molecules 2016, 21(8), 970; https://doi.org/10.3390/molecules21080970 - 25 Jul 2016

Cited by 31 | Viewed by 6044

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 2–8 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 1–7 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 Chemistry)

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9 pages, 987 KiB

Open AccessArticle

Quorum Sensing Inhibition and Structure–Activity Relationships of β-Keto Esters

by Stephanie Forschner-Dancause, Emily Poulin and Susan Meschwitz

Molecules 2016, 21(8), 971; https://doi.org/10.3390/molecules21080971 - 25 Jul 2016

Cited by 19 | Viewed by 6914

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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13 pages, 2405 KiB

Open AccessArticle

Immobilization of Chlamydomonas reinhardtii CLH1 on APTES-Coated Magnetic Iron Oxide Nanoparticles and Its Potential in the Production of Chlorophyll Derivatives

by Chih-Chung Yen, Yao-Chen Chuang, Chia-Yun Ko, Long-Fang O. Chen, Sheau-Shyang Chen, Chia-Jung Lin, Yi-Li Chou and Jei-Fu Shaw

Molecules 2016, 21(8), 972; https://doi.org/10.3390/molecules21080972 - 26 Jul 2016

Cited by 11 | Viewed by 6499

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

(This article belongs to the Special Issue Recent Developments in Using Biocatalysts and Whole Cells for Organic Synthesis)

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13 pages, 2436 KiB

Open AccessArticle

Estrogen Receptor Signaling and the PI3K/Akt Pathway Are Involved in Betulinic Acid-Induced eNOS Activation

by Nicolas Hohmann, Ning Xia, Katja Steinkamp-Fenske, Ulrich Förstermann and Huige Li

Molecules 2016, 21(8), 973; https://doi.org/10.3390/molecules21080973 - 25 Jul 2016

Cited by 25 | Viewed by 7930

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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15 pages, 3159 KiB

Open AccessArticle

Corynoline Isolated from Corydalis bungeana Turcz. Exhibits Anti-Inflammatory Effects via Modulation of Nfr2 and MAPKs

by Chunjuan Yang, Chengyue Zhang, Zhibin Wang, Zhenqiu Tang, Haixue Kuang and Ah-Ng Tony Kong

Molecules 2016, 21(8), 975; https://doi.org/10.3390/molecules21080975 - 27 Jul 2016

Cited by 39 | Viewed by 6361

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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14 pages, 2753 KiB

Open AccessArticle

Efficacy of Acetylshikonin in Preventing Obesity and Hepatic Steatosis in db/db Mice

by Mei-Ling Su, Yu He, Qi-Sen Li and Bang-Hao Zhu

Molecules 2016, 21(8), 976; https://doi.org/10.3390/molecules21080976 - 28 Jul 2016

Cited by 37 | Viewed by 7709

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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11 pages, 689 KiB

Open AccessArticle

Efficient Double Suzuki Cross-Coupling Reactions of 2,5-Dibromo-3-hexylthiophene: Anti-Tumor, Haemolytic, Anti-Thrombolytic and Biofilm Inhibition Studies

by Hafiz Mansoor Ikram, Nasir Rasool, Muhammad Zubair, Khalid Mohammed Khan, Ghayoor Abbas Chotana, Muhammad Nadeem Akhtar, Nadiah Abu, Noorjahan Banu Alitheen, Abdallah Mohamed Elgorban and Usman Ali Rana

Molecules 2016, 21(8), 977; https://doi.org/10.3390/molecules21080977 - 27 Jul 2016

Cited by 17 | Viewed by 6382

Abstract

The present study describes several novel 2,5-biaryl-3-hexylthiophene derivatives (3a–i) 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 (3a–i) 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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13 pages, 6888 KiB

Open AccessArticle

Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2

by Qiaolin Dong, Ju Luo, Wen Qiu, Li Cai, Syed Ishtiaq Anjum, Bin Li, Mingsheng Hou, Guanlin Xie and Guochang Sun

Molecules 2016, 21(8), 978; https://doi.org/10.3390/molecules21080978 - 27 Jul 2016

Cited by 17 | Viewed by 6866

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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10 pages, 2842 KiB

Open AccessArticle

Lutein, a Natural Carotenoid, Induces α-1,3-Glucan Accumulation on the Cell Wall Surface of Fungal Plant Pathogens

by Junnosuke Otaka, Shigemi Seo and Marie Nishimura

Molecules 2016, 21(8), 980; https://doi.org/10.3390/molecules21080980 - 28 Jul 2016

Cited by 24 | Viewed by 7176

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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12 pages, 2326 KiB

Open AccessCommunication

N,N′-Bis(2-cyclohexylethyl)naphtho[2,3-b:6,7-b′]dithiophene Diimides: Effects of Substituents

by Masahiro Nakano, Daisuke Hashizume and Kazuo Takimiya

Molecules 2016, 21(8), 981; https://doi.org/10.3390/molecules21080981 - 28 Jul 2016

Cited by 10 | Viewed by 6685

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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14 pages, 3556 KiB

Open AccessArticle

Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the Chemosensitivity of Tumor Cells to Paclitaxel

by Joana Fonseca, Sandra Marques, Patrícia M. A. Silva, Pedro Brandão, Honorina Cidade, Madalena M. Pinto and Hassan Bousbaa

Molecules 2016, 21(8), 982; https://doi.org/10.3390/molecules21080982 - 29 Jul 2016

Cited by 16 | Viewed by 6916

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 [...] Read more.

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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11 pages, 379 KiB

Open AccessArticle

Bioactive Molecule Prediction Using Extreme Gradient Boosting

by Ismail Babajide Mustapha and Faisal Saeed

Molecules 2016, 21(8), 983; https://doi.org/10.3390/molecules21080983 - 28 Jul 2016

Cited by 193 | Viewed by 12719

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 [...] Read more.

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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15 pages, 2088 KiB

Open AccessArticle

Influences of Adhesion Variability on the “Living” Dynamics of Filamentous Bacteria in Microfluidic Channels

by Justin P. Jahnke, Jessica L. Terrell, Austin M. Smith, Xuanhong Cheng and Dimitra N. Stratis-Cullum

Molecules 2016, 21(8), 985; https://doi.org/10.3390/molecules21080985 - 28 Jul 2016

Cited by 9 | Viewed by 8563

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 [...] Read more.

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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5 pages, 4888 KiB

Open AccessArticle

A Well-Defined {[(PhCH₂O)₂P(CH₃)₂CHNCH(CH₃)₂]₂PdCl₂} Complex Catalyzed Hiyama Coupling of Aryl Bromides with Arylsilanes

by Mengping Guo, Leiqing Fu, Jiamin Li, Lanjiang Zhou and Yanping Kang

Molecules 2016, 21(8), 987; https://doi.org/10.3390/molecules21080987 - 29 Jul 2016

Cited by 2 | Viewed by 4732

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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10 pages, 1687 KiB

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

by Aurélien A. M. Peru, Amandine L. Flourat, Christian Gunawan, Warwick Raverty, Martyn Jevric, Ben W. Greatrex and Florent Allais

Molecules 2016, 21(8), 988; https://doi.org/10.3390/molecules21080988 - 29 Jul 2016

Cited by 23 | Viewed by 8875

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 [...] Read more.

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

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

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14 pages, 5383 KiB

Open AccessArticle

Selective Extraction of Flavonoids from Sophora flavescens Ait. by Mechanochemistry

by Qihong Zhang, Jingbo Yu, Yingyao Wang and Weike Su

Molecules 2016, 21(8), 989; https://doi.org/10.3390/molecules21080989 - 29 Jul 2016

Cited by 18 | Viewed by 6963

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 [...] Read more.

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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11 pages, 2904 KiB

Open AccessArticle

Isolation of a Cyclic (Alkyl)(amino)germylene

by Liliang Wang, Yi Shan Lim, Yongxin Li, Rakesh Ganguly and Rei Kinjo

Molecules 2016, 21(8), 990; https://doi.org/10.3390/molecules21080990 - 29 Jul 2016

Cited by 27 | Viewed by 10168

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 [...] Read more.

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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15 pages, 1136 KiB

Open AccessArticle

In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi-Synthetic Spirosteroid Analogues

by Laura García-Pupo, Armando Zaldo-Castro, Vassiliki Exarchou, Juan Enrique Tacoronte-Morales, Luc Pieters, Wim Vanden Berghe, Yanier Nuñez-Figueredo and René Delgado-Hernández

Molecules 2016, 21(8), 992; https://doi.org/10.3390/molecules21080992 - 29 Jul 2016

Cited by 8 | Viewed by 5718

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 [...] Read more.

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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13 pages, 2583 KiB

Open AccessArticle

Chemical Composition and Inhibitory Effect of Lentinula edodes Ethanolic Extract on Experimentally Induced Atopic Dermatitis in Vitro and in Vivo

by Eun-Ju Choi, Zee-Yong Park and Eun-Kyung Kim

Molecules 2016, 21(8), 993; https://doi.org/10.3390/molecules21080993 - 29 Jul 2016

Cited by 21 | Viewed by 9687

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 [...] Read more.

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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12 pages, 1629 KiB

Open AccessArticle

Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies

by Aleksandra Mędra, Magdalena Witkowska, Agata Majchrzak, Barbara Cebula-Obrzut, Michael Y. Bonner, Tadeusz Robak, Jack L. Arbiser and Piotr Smolewski

Molecules 2016, 21(8), 995; https://doi.org/10.3390/molecules21080995 - 30 Jul 2016

Cited by 5 | Viewed by 5438

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 [...] Read more.

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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14 pages, 730 KiB

Open AccessArticle

Antioxidant Capacities of Fractions of Bamboo Shaving Extract and Their Antioxidant Components

by Jinyan Gong, Jun Huang, Gongnian Xiao, Feng Chen, Bolim Lee, Qing Ge, Yuru You, Shiwang Liu and Ying Zhang

Molecules 2016, 21(8), 996; https://doi.org/10.3390/molecules21080996 - 30 Jul 2016

Cited by 34 | Viewed by 7246

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: [...] Read more.

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 Chemistry)

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14 pages, 5596 KiB

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

by Soundharrajan Ilavenil, Da Hye Kim, Srisesharam Srigopalram, Mariadhas Valan Arasu, Kyung Dong Lee, Jeong Chae Lee, Jong Suk Lee, Senthil Renganathan and Ki Choon Choi

Molecules 2016, 21(8), 997; https://doi.org/10.3390/molecules21080997 - 2 Aug 2016

Cited by 38 | Viewed by 7279

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 [...] Read more.

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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15 pages, 2014 KiB

Open AccessArticle

Agavins Increase Neurotrophic Factors and Decrease Oxidative Stress in the Brains of High-Fat Diet-Induced Obese Mice

by Elena Franco-Robles and Mercedes G. López

Molecules 2016, 21(8), 998; https://doi.org/10.3390/molecules21080998 - 2 Aug 2016

Cited by 36 | Viewed by 9910

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 [...] Read more.

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 Glycosciences)

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7 pages, 921 KiB

Open AccessArticle

Intramolecular Chain Hydrosilylation of Alkynylphenylsilanes Using a Silyl Cation as a Chain Carrier

by Hidekazu Arii, Kenichi Nakabayashi, Kunio Mochida and Takayuki Kawashima

Molecules 2016, 21(8), 999; https://doi.org/10.3390/molecules21080999 - 1 Aug 2016

Cited by 28 | Viewed by 5609

Abstract

Diorganyl[2-(trimethylsilylethynyl)phenyl]silanes 1a–c 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 (2a–e) in moderate to good yields. However, no reaction [...] Read more.

Diorganyl[2-(trimethylsilylethynyl)phenyl]silanes 1a–c 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 (2a–e) 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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14 pages, 3675 KiB

Open AccessArticle

A General Catalytic Enantioselective Transfer Hydrogenation Reaction of β,β-Disubstituted Nitroalkenes Promoted by a Simple Organocatalyst

by Luca Bernardi and Mariafrancesca Fochi

Molecules 2016, 21(8), 1000; https://doi.org/10.3390/molecules21081000 - 30 Jul 2016

Cited by 13 | Viewed by 7079

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 [...] Read more.

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

(This article belongs to the Special Issue Recent Synthetic Aspects on the Chemistry of Nitro, Nitroso and Amino Compounds)

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13 pages, 2843 KiB

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.

by Desong Wu, Qi Yao, Yajuan Chen, Xiaodong Hu, Chen Qing and Minghua Qiu

Molecules 2016, 21(8), 1001; https://doi.org/10.3390/molecules21081001 - 30 Jul 2016

Cited by 16 | Viewed by 5229

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 [...] Read more.

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 Chemistry)

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14 pages, 16980 KiB

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

by Mika Ishigaki, Yui Yasui, Paralee Puangchit, Shoya Kawasaki and Yukihiro Ozaki

Molecules 2016, 21(8), 1003; https://doi.org/10.3390/molecules21081003 - 1 Aug 2016

Cited by 23 | Viewed by 6303

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 [...] Read more.

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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10 pages, 2402 KiB

Open AccessArticle

Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents

by Mehlika Dilek Altıntop, Özgür Devrim Can, Ümide Demir Özkay and Zafer Asım Kaplancıklı

Molecules 2016, 21(8), 1004; https://doi.org/10.3390/molecules21081004 - 1 Aug 2016

Cited by 24 | Viewed by 6036

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. [...] Read more.

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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8 pages, 2851 KiB

Open AccessArticle

Preparation of Hydrochlorothiazide Nanoparticles for Solubility Enhancement

by Eliska Vaculikova, Aneta Cernikova, Daniela Placha, Martin Pisarcik, Pavlina Peikertova, Katerina Dedkova, Ferdinand Devinsky and Josef Jampilek

Molecules 2016, 21(8), 1005; https://doi.org/10.3390/molecules21081005 - 2 Aug 2016

Cited by 22 | Viewed by 8287

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 [...] Read more.

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

(This article belongs to the Special Issue Nanobiostructures: Commemorative Issue in Honor of Professor Serban Solacolu (1905-1980) - Founder of the Romanian School of Oxide Materials Science and Engineering)

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15 pages, 744 KiB

Open AccessArticle

Phenolic and Volatile Composition of a Dry Spearmint (Mentha spicata L.) Extract

by Martina Cirlini, Pedro Mena, Michele Tassotti, Kelli A. Herrlinger, Kristin M. Nieman, Chiara Dall’Asta and Daniele Del Rio

Molecules 2016, 21(8), 1007; https://doi.org/10.3390/molecules21081007 - 3 Aug 2016

Cited by 112 | Viewed by 13646

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 [...] Read more.

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

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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11 pages, 1303 KiB

Open AccessArticle

In Vivo Release Kinetics and Antibacterial Activity of Novel Polyphenols-Enriched Chewing Gums

by Gianmaria Fabrizio Ferrazzano, Tiziana Cantile, Marco Coda, Brunella Alcidi, Giancarla Sangianantoni, Aniello Ingenito, Michele Di Stasio and Maria Grazia Volpe

Molecules 2016, 21(8), 1008; https://doi.org/10.3390/molecules21081008 - 2 Aug 2016

Cited by 21 | Viewed by 5691

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 [...] Read more.

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

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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13 pages, 1625 KiB

Open AccessArticle

Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin Metabolites, in Human Aortic Endothelial Cells

by Valentina Spigoni, Pedro Mena, Monia Cito, Federica Fantuzzi, Riccardo C. Bonadonna, Furio Brighenti, Alessandra Dei Cas and Daniele Del Rio

Molecules 2016, 21(8), 1009; https://doi.org/10.3390/molecules21081009 - 2 Aug 2016

Cited by 45 | Viewed by 7665

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 [...] Read more.

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

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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26 pages, 2245 KiB

Open AccessArticle

Synthesis, Biological Profiling and Determination of the Tubulin-Bound Conformation of 12-Aza-Epothilones (Azathilones)

by Andrea Jantsch, Lidia Nieto, Jürg Gertsch, Javier Rodríguez-Salarichs, Ruth Matesanz, Jesús Jiménez-Barbero, J. Fernando Díaz, Ángeles Canales and Karl-Heinz Altmann

Molecules 2016, 21(8), 1010; https://doi.org/10.3390/molecules21081010 - 3 Aug 2016

Cited by 7 | Viewed by 5672

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 [...] Read more.

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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16 pages, 1172 KiB

Open AccessArticle

Struvite Precipitation as a Means of Recovering Nutrients and Mitigating Ammonia Toxicity in a Two-Stage Anaerobic Digester Treating Protein-Rich Feedstocks

by Shunli Wang, Gary L. Hawkins, Brian H. Kiepper and Keshav C. Das

Molecules 2016, 21(8), 1011; https://doi.org/10.3390/molecules21081011 - 3 Aug 2016

Cited by 16 | Viewed by 5997

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 [...] Read more.

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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21 pages, 3933 KiB

Open AccessArticle

Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors

by Hai-Chao Wang, Xiao-Qiang Yan, Tian-Long Yan, Hong-Xia Li, Zhong-Chang Wang and Hai-Liang Zhu

Molecules 2016, 21(8), 1012; https://doi.org/10.3390/molecules21081012 - 3 Aug 2016

Cited by 20 | Viewed by 7740

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 [...] Read more.

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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15 pages, 1846 KiB

Open AccessArticle

Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines

by Omar Aristeo Peña-Morán, María Luisa Villarreal, Laura Álvarez-Berber, Angélica Meneses-Acosta and Verónica Rodríguez-López

Molecules 2016, 21(8), 1013; https://doi.org/10.3390/molecules21081013 - 4 Aug 2016

Cited by 192 | Viewed by 8490

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 [...] Read more.

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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11 pages, 2213 KiB

Open AccessArticle

The Herbal Medicine KIOM-MA128 Inhibits the Antigen/IgE-Mediated Allergic Response in Vitro and in Vivo

by Kwang Il Park, Dong Gun Kim, Jae Myung Yoo and Jin Yeul Ma

Molecules 2016, 21(8), 1015; https://doi.org/10.3390/molecules21081015 - 4 Aug 2016

Cited by 13 | Viewed by 7446

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 [...] Read more.

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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10 pages, 2905 KiB

Open AccessArticle

Preparative Separation of Phenolic Compounds from Chimonanthus praecox Flowers by High-Speed Counter-Current Chromatography Using a Stepwise Elution Mode

by Huaizhi Li, Yongqing Zhang, Qian Liu, Changlei Sun, Jia Li, Peng Yang and Xiao Wang

Molecules 2016, 21(8), 1016; https://doi.org/10.3390/molecules21081016 - 4 Aug 2016

Cited by 36 | Viewed by 6829

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) [...] Read more.

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 a–d and f were the first separated and reported from the Chimonanthus praecox flower extract. Full article

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16 pages, 2664 KiB

Open AccessArticle

Laccase Gene Family in Cerrena sp. HYB07: Sequences, Heterologous Expression and Transcriptional Analysis

by Jie Yang, Xinqi Xu, Tzi Bun Ng, Juan Lin and Xiuyun Ye

Molecules 2016, 21(8), 1017; https://doi.org/10.3390/molecules21081017 - 4 Aug 2016

Cited by 19 | Viewed by 6375

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 [...] Read more.

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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17 pages, 5073 KiB

Open AccessArticle

Modulation of Neural Network Activity through Single Cell Ablation: An in Vitro Model of Minimally Invasive Neurosurgery

by Alessandro Soloperto, Marta Bisio, Gemma Palazzolo, Michela Chiappalone, Paolo Bonifazi and Francesco Difato

Molecules 2016, 21(8), 1018; https://doi.org/10.3390/molecules21081018 - 5 Aug 2016

Cited by 6 | Viewed by 5543

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 [...] Read more.

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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10 pages, 2589 KiB

Open AccessArticle

Optimization and Biodistribution of [¹¹C]-TKF, An Analog of Tau Protein Imaging Agent [¹⁸F]-THK523

by Yanyan Kong, Yihui Guan, Fengchun Hua, Zhengwei Zhang, Xiuhong Lu, Tengfang Zhu, Bizeng Zhao, Jianhua Zhu, Cong Li and Jian Chen

Molecules 2016, 21(8), 1019; https://doi.org/10.3390/molecules21081019 - 5 Aug 2016

Cited by 3 | Viewed by 5253

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 [...] Read more.

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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13 pages, 2874 KiB

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

by Smaail Radi, Ahmed Attayibat, Mohamed El-Massaoudi, Amin Salhi, Driss Eddike, Monique Tillard and Yahia N. Mabkhot

Molecules 2016, 21(8), 1020; https://doi.org/10.3390/molecules21081020 - 5 Aug 2016

Cited by 8 | Viewed by 5679

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* [...] Read more.

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

(This article belongs to the Special Issue Density Functional Theory and Reactivity Indices: Applications in Organic Chemical Reactivity)

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13 pages, 11692 KiB

Open AccessArticle

Siegesbeckia orientalis Extract Inhibits TGFβ1-Induced Migration and Invasion of Endometrial Cancer Cells

by Chi-Chang Chang, Xue-Hua Ling, Hsia-Fen Hsu, Jing-Mei Wu, Chao-Ping Wang, Jyh-Ferng Yang, Li-Wen Fang and Jer-Yiing Houng

Molecules 2016, 21(8), 1021; https://doi.org/10.3390/molecules21081021 - 5 Aug 2016

Cited by 20 | Viewed by 7955

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 [...] Read more.

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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8 pages, 1296 KiB

Open AccessCommunication

Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice

by Dong Wook Lim, Hyun Jung Son, Min Young Um, In-Ho Kim, Daeseok Han, Suengmok Cho and Chang-Ho Lee

Molecules 2016, 21(8), 1022; https://doi.org/10.3390/molecules21081022 - 5 Aug 2016

Cited by 23 | Viewed by 6072

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 [...] Read more.

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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9 pages, 3420 KiB

Open AccessArticle

A Simple and Effective Ratiometric Fluorescent Probe for the Selective Detection of Cysteine and Homocysteine in Aqueous Media

by Risong Na, Meiqing Zhu, Shisuo Fan, Zhen Wang, Xiangwei Wu, Jun Tang, Jia Liu, Yi Wang and Rimao Hua

Molecules 2016, 21(8), 1023; https://doi.org/10.3390/molecules21081023 - 5 Aug 2016

Cited by 26 | Viewed by 7193

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 [...] Read more.

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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13 pages, 1224 KiB

Open AccessArticle

Variations in Essential Oil Yield, Composition, and Antioxidant Activity of Different Plant Organs from Blumea balsamifera (L.) DC. at Different Growth Times

by Yuan Yuan, Mei Huang, Yu-Xin Pang, Fu-Lai Yu, Ce Chen, Li-Wei Liu, Zhen-Xia Chen, Ying-Bo Zhang, Xiao-Lu Chen and Xuan Hu

Molecules 2016, 21(8), 1024; https://doi.org/10.3390/molecules21081024 - 5 Aug 2016

Cited by 53 | Viewed by 8530

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 [...] Read more.

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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9 pages, 2641 KiB

Open AccessArticle

Porphyrin Dye-Sensitized Zinc Oxide Aggregated Anodes for Use in Solar Cells

by Yu-Kai Syu, Yogesh Tingare, Shou-Yen Lin, Chen-Yu Yeh and Jih-Jen Wu

Molecules 2016, 21(8), 1025; https://doi.org/10.3390/molecules21081025 - 5 Aug 2016

Cited by 13 | Viewed by 5409

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 [...] Read more.

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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18 pages, 3744 KiB

Open AccessArticle

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats

by Muhammad Tayyab Akhtar, Mohamad Syakir Bin Mohd Sarib, Intan Safinar Ismail, Faridah Abas, Amin Ismail, Nordin Hj Lajis and Khozirah Shaari

Molecules 2016, 21(8), 1026; https://doi.org/10.3390/molecules21081026 - 9 Aug 2016

Cited by 35 | Viewed by 14754

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 [...] Read more.

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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12 pages, 1880 KiB

Open AccessCommunication

Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists

by Nuno A. L. Pereira, Francesc X. Sureda, Maria Pérez, Mercedes Amat and Maria M. M. Santos

Molecules 2016, 21(8), 1027; https://doi.org/10.3390/molecules21081027 - 6 Aug 2016

Cited by 4 | Viewed by 6339

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 [...] Read more.

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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26 pages, 6027 KiB

Open AccessArticle

Glutamine Synthetase Drugability beyond Its Active Site: Exploring Oligomerization Interfaces and Pockets

by Cátia Moreira, Maria J. Ramos and Pedro A. Fernandes

Molecules 2016, 21(8), 1028; https://doi.org/10.3390/molecules21081028 - 8 Aug 2016

Cited by 12 | Viewed by 7463

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 [...] Read more.

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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13 pages, 2061 KiB

Open AccessArticle

The Complete Chloroplast Genome Sequence of the Medicinal Plant Swertia mussotii Using the PacBio RS II Platform

by Beibei Xiang, Xiaoxue Li, Jun Qian, Lizhi Wang, Lin Ma, Xiaoxuan Tian and Yong Wang

Molecules 2016, 21(8), 1029; https://doi.org/10.3390/molecules21081029 - 9 Aug 2016

Cited by 44 | Viewed by 6390

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 [...] Read more.

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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15 pages, 6520 KiB

Open AccessArticle

TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds

by Satoru Matsukawa, Junya Kimura and Miki Yoshioka

Molecules 2016, 21(8), 1030; https://doi.org/10.3390/molecules21081030 - 10 Aug 2016

Cited by 7 | Viewed by 7070

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 [...] Read more.

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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12 pages, 4261 KiB

Open AccessArticle

New Sesquiterpenenoids from Ainsliaea yunnanensis

by Xiang-Lei Wu, Xiao-Juan Xiong, Wen-Quan Lu, Hao Huang, Yun-Heng Shen, Zhi-Jun Wu and Wan-Sheng Chen

Molecules 2016, 21(8), 1031; https://doi.org/10.3390/molecules21081031 - 8 Aug 2016

Cited by 14 | Viewed by 4465

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 (1–4), together with seven known dimeric sesquiterpene lactones (5–11) and ten [...] Read more.

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 (1–4), together with seven known dimeric sesquiterpene lactones (5–11) and ten sesquiterpenes (12–21). Their structures were elucidated by spectroscopic methods. The relative stereochemistry of ainsliadimer F was further confirmed by single crystal X-ray diffraction analysis. Compounds 1–21 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 Chemistry)

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15 pages, 2660 KiB

Open AccessArticle

Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

by Yao Zhu, Ya-Jie Zhang, Wei-Wei Liu, Ai-Wu Shi and Ning Gu

Molecules 2016, 21(8), 1033; https://doi.org/10.3390/molecules21081033 - 9 Aug 2016

Cited by 71 | Viewed by 8406

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 [...] Read more.

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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17 pages, 1110 KiB

Open AccessArticle

Phytoestrogen Metabolism by Adult Human Gut Microbiota

by Pilar Gaya, Margarita Medina, Abel Sánchez-Jiménez and José Mᵃ Landete

Molecules 2016, 21(8), 1034; https://doi.org/10.3390/molecules21081034 - 9 Aug 2016

Cited by 120 | Viewed by 11209

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 [...] Read more.

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

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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9 pages, 919 KiB

Open AccessArticle

Synthesis and Structure-Activity Relationship of Some New Thiophene-Based Heterocycles as Potential Antimicrobial Agents

by Yahia Nasser Mabkhot, Fatima Alatibi, Nahed Nasser E. El-Sayed, Nabila Abdelshafy Kheder and Salim S. Al-Showiman

Molecules 2016, 21(8), 1036; https://doi.org/10.3390/molecules21081036 - 9 Aug 2016

Cited by 54 | Viewed by 6270

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 [...] Read more.

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 Chemistry)

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19 pages, 3467 KiB

Open AccessArticle

Predicting Protein-Protein Interactions Using BiGGER: Case Studies

by Rui M. Almeida, Simone Dell’Acqua, Ludwig Krippahl, José J. G. Moura and Sofia R. Pauleta

Molecules 2016, 21(8), 1037; https://doi.org/10.3390/molecules21081037 - 9 Aug 2016

Cited by 8 | Viewed by 6547

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 [...] Read more.

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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12 pages, 1448 KiB

Open AccessArticle

Chemo-Enzymatic Synthesis of Oligoglycerol Derivatives

by Abhishek K. Singh, Remi Nguyen, Nicolas Galy, Rainer Haag, Sunil K. Sharma and Christophe Len

Molecules 2016, 21(8), 1038; https://doi.org/10.3390/molecules21081038 - 9 Aug 2016

Cited by 13 | Viewed by 5490

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 [...] Read more.

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

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

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11 pages, 1329 KiB

Open AccessArticle

Insecticidal Properties of a Highly Potent Wax Isolated from Dolichandra cynanchoides Cham

by Georgina Díaz Napal, María C. Carpinella and Sara M. Palacios

Molecules 2016, 21(8), 1039; https://doi.org/10.3390/molecules21081039 - 11 Aug 2016

Cited by 7 | Viewed by 4236

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 [...] Read more.

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 Chemistry)

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12 pages, 4177 KiB

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

by Huarong Xu, Ran Liu, Bosai He, Cathy Wenchuan Bi, Kaishun Bi and Qing Li

Molecules 2016, 21(8), 1040; https://doi.org/10.3390/molecules21081040 - 10 Aug 2016

Cited by 51 | Viewed by 8974

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 [...] Read more.

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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10 pages, 1927 KiB

Open AccessArticle

Synthesis and Characterization of Process-Related Impurities of Antidiabetic Drug Linagliptin

by Yiwen Huang, Xiaoqing He, Taizhi Wu and Fuli Zhang

Molecules 2016, 21(8), 1041; https://doi.org/10.3390/molecules21081041 - 9 Aug 2016

Cited by 16 | Viewed by 12937

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 [...] Read more.

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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13 pages, 5046 KiB

Open AccessCommunication

Pd@[nBu₄][Br] as a Simple Catalytic System for N-Alkylation Reactions with Alcohols

by Bastien Cacciuttolo, Oana Pascu, Cyril Aymonier and Mathieu Pucheault

Molecules 2016, 21(8), 1042; https://doi.org/10.3390/molecules21081042 - 10 Aug 2016

Cited by 5 | Viewed by 5676

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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8 pages, 1044 KiB

Open AccessArticle

A Versatile Axle for the Construction of Disassemblage Rotaxanes

by Lucas A. Powers and David B. Smithrud

Molecules 2016, 21(8), 1043; https://doi.org/10.3390/molecules21081043 - 10 Aug 2016

Cited by 3 | Viewed by 3722

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. [...] Read more.

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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10 pages, 1956 KiB

Open AccessArticle

Catalytic Oxidation of Phenol and 2,4-Dichlorophenol by Using Horseradish Peroxidase Immobilized on Graphene Oxide/Fe₃O₄

by Qing Chang, Jia Huang, Yaobin Ding and Heqing Tang

Molecules 2016, 21(8), 1044; https://doi.org/10.3390/molecules21081044 - 10 Aug 2016

Cited by 64 | Viewed by 7037

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 [...] Read more.

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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10 pages, 387 KiB

Open AccessCommunication

In Vitro Antileishmanial Activity of Sterols from Trametes versicolor (Bres. Rivarden)

by Vivian Leliebre-Lara, Lianet Monzote Fidalgo, Eva-Maria Pferschy-Wenzig, Olaf Kunert, Clara Nogueiras Lima and Rudolf Bauer

Molecules 2016, 21(8), 1045; https://doi.org/10.3390/molecules21081045 - 10 Aug 2016

Cited by 32 | Viewed by 6777

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 [...] Read more.

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

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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11 pages, 2539 KiB

Open AccessArticle

Anti-Inflammatory Effects of 6,8-Diprenyl-7,4′-dihydroxyflavanone from Sophora tonkinensis on Lipopolysaccharide-Stimulated RAW 264.7 Cells

by Hee-Sung Chae, Hunseung Yoo, Young-Mi Kim, Young Hee Choi, Chang Hoon Lee and Young-Won Chin

Molecules 2016, 21(8), 1049; https://doi.org/10.3390/molecules21081049 - 11 Aug 2016

Cited by 24 | Viewed by 5162 | Correction

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 [...] Read more.

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 Chemistry)

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12 pages, 1001 KiB

Open AccessArticle

Achillea schurii Flowers: Chemical, Antioxidant, and Antimicrobial Investigations

by Daniela Benedec, Daniela Hanganu, Ilioara Oniga, Lorena Filip, Cristina Bischin, Radu Silaghi-Dumitrescu, Brînduşa Tiperciuc and Laurian Vlase

Molecules 2016, 21(8), 1050; https://doi.org/10.3390/molecules21081050 - 12 Aug 2016

Cited by 38 | Viewed by 5879

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 [...] Read more.

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 Chemistry)

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11 pages, 955 KiB

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

by Rajalingam Agneeswari, Ji Yeong Sung, Eun Sol Jo, Hee Young Jeon, Vellaiappillai Tamilavan and Myung Ho Hyun

Molecules 2016, 21(8), 1051; https://doi.org/10.3390/molecules21081051 - 12 Aug 2016

Cited by 6 | Viewed by 4734

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 [...] Read more.

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

(This article belongs to the Special Issue Chromatographic Separation of Enantiomers: Commemorative Issue in Honor of Professor Stig Allenmark on the Occasion of His 80th Birthday)

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11 pages, 701 KiB

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

by Yu Fen Zheng, Jee Sun Min, Doyun Kim, Jung Bae Park, Sung-Wook Choi, Eun Seong Lee, Kun Na and Soo Kyung Bae

Molecules 2016, 21(8), 1052; https://doi.org/10.3390/molecules21081052 - 12 Aug 2016

Cited by 15 | Viewed by 5796

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 [...] Read more.

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 (K_i, 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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16 pages, 2138 KiB

Open AccessArticle

Synthesis and Evaluation of Bicyclo[3.1.0]hexane-Based UDP-Galf Analogues as Inhibitors of the Mycobacterial Galactofuranosyltransferase GlfT2

by Todd L. Lowary and Jing Li

Molecules 2016, 21(8), 1053; https://doi.org/10.3390/molecules21081053 - 12 Aug 2016

Cited by 4 | Viewed by 6020

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 [...] Read more.

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 Chemistry)

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24 pages, 4008 KiB

Open AccessArticle

Aryloxyalkanoic Acids as Non-Covalent Modifiers of the Allosteric Properties of Hemoglobin

by Abdelsattar M. Omar, Mona A. Mahran, Mohini S. Ghatge, Faida H. A. Bamane, Mostafa H. Ahmed, Moustafa E. El-Araby, Osheiza Abdulmalik and Martin K. Safo

Molecules 2016, 21(8), 1057; https://doi.org/10.3390/molecules21081057 - 13 Aug 2016

Cited by 5 | Viewed by 5593

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 [...] Read more.

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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10 pages, 1142 KiB

Open AccessArticle

Synthesis of Natural Homoisoflavonoids Having Either 5,7-Dihydroxy-6-methoxy or 7-Hydroxy-5,6-dimethoxy Groups

by Hyungjun Lee, Yue Yuan, Inmoo Rhee, Timothy W. Corson and Seung-Yong Seo

Molecules 2016, 21(8), 1058; https://doi.org/10.3390/molecules21081058 - 13 Aug 2016

Cited by 12 | Viewed by 7571

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 [...] Read more.

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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13 pages, 3416 KiB

Open AccessArticle

Punica granatum L. Hydrogel for Wound Care Treatment: From Case Study to Phytomedicine Standardization

by Aline Fleck, Patrik F. G. Cabral, Felipe F. M. Vieira, Deo A. Pinheiro, Carlos R. Pereira, Wilson C. Santos and Thelma B. Machado

Molecules 2016, 21(8), 1059; https://doi.org/10.3390/molecules21081059 - 22 Aug 2016

Cited by 32 | Viewed by 9584

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 [...] Read more.

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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10 pages, 9478 KiB

Open AccessArticle

Efficient Enzyme-Free Biomimetic Sensors for Natural Phenol Detection

by Luane Ferreira Garcia, Aparecido Ribeiro Souza, Germán Sanz Lobón, Wallans Torres Pio Dos Santos, Morgana Fernandes Alecrim, Mariângela Fontes Santiago, Rafael Luque Álvarez De Sotomayor and Eric De Souza Gil

Molecules 2016, 21(8), 1060; https://doi.org/10.3390/molecules21081060 - 13 Aug 2016

Cited by 5 | Viewed by 5573

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 [...] Read more.

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

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

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15 pages, 6451 KiB

Open AccessArticle

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway

by Chongshan Dai, Daowen Li, Lijing Gong, Xilong Xiao and Shusheng Tang

Molecules 2016, 21(8), 1061; https://doi.org/10.3390/molecules21081061 - 22 Aug 2016

Cited by 53 | Viewed by 8435

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 [...] Read more.

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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12 pages, 5287 KiB

Open AccessArticle

Influence of Cysteine and Tryptophan Substitution on DNA-Binding Activity on Maize α-Hairpinin Antimicrobial Peptide

by Daniel A. Sousa, William F. Porto, Maria Z. Silva, Tatiane R. Da Silva and Octávio L. Franco

Molecules 2016, 21(8), 1062; https://doi.org/10.3390/molecules21081062 - 13 Aug 2016

Cited by 37 | Viewed by 6389

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 [...] Read more.

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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19 pages, 2901 KiB

Open AccessArticle

Physicochemical Changes and Resistant-Starch Content of Extruded Cornstarch with and without Storage at Refrigerator Temperatures

by David Neder-Suárez, Carlos A. Amaya-Guerra, Armando Quintero-Ramos, Esther Pérez-Carrillo, María G. de J. Alanís-Guzmán, Juan G. Báez-González, Carlos L. García-Díaz, María A. Núñez-González, Daniel Lardizábal-Gutiérrez and Jorge A. Jiménez-Castro

Molecules 2016, 21(8), 1064; https://doi.org/10.3390/molecules21081064 - 15 Aug 2016

Cited by 27 | Viewed by 7936

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 [...] Read more.

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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14 pages, 250 KiB

Open AccessArticle

Biological Activities of the Essential Oil from Erigeron floribundus

by Riccardo Petrelli, Giuseppe Orsomando, Leonardo Sorci, Filippo Maggi, Farahnaz Ranjbarian, Prosper C. Biapa Nya, Dezemona Petrelli, Luca A. Vitali, Giulio Lupidi, Luana Quassinti, Massimo Bramucci, Anders Hofer and Loredana Cappellacci

Molecules 2016, 21(8), 1065; https://doi.org/10.3390/molecules21081065 - 13 Aug 2016

Cited by 28 | Viewed by 9508

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 [...] Read more.

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 Chemistry)

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9 pages, 4531 KiB

Open AccessArticle

Magnetic, Fluorescence and Transition Metal Ion Response Properties of 2,6-Diaminopyridine Modified Silica-Coated Fe₃O₄ Nanoparticles

by Yunhui Zhai, Ruijuan Song, Changhu Zhang, Qun He, Quan Han and Yingjuan Qu

Molecules 2016, 21(8), 1066; https://doi.org/10.3390/molecules21081066 - 15 Aug 2016

Cited by 3 | Viewed by 5011

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 [...] Read more.

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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12 pages, 1935 KiB

Open AccessArticle

Rapid Isolation and Determination of Flavones in Biological Samples Using Zinc Complexation Coupled with High-Performance Liquid Chromatography

by Chenghe Sun, Hecheng Wang, Yingping Wang and Shengyuan Xiao

Molecules 2016, 21(8), 1067; https://doi.org/10.3390/molecules21081067 - 16 Aug 2016

Cited by 4 | Viewed by 5297

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 [...] Read more.

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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18 pages, 1120 KiB

Open AccessArticle

N-Alkoxyphenylhydroxynaphthalenecarboxamides and Their Antimycobacterial Activity

by Tomas Gonec, Sarka Pospisilova, Tereza Kauerova, Jiri Kos, Jana Dohanosova, Michal Oravec, Peter Kollar, Aidan Coffey, Tibor Liptaj, Alois Cizek and Josef Jampilek

Molecules 2016, 21(8), 1068; https://doi.org/10.3390/molecules21081068 - 16 Aug 2016

Cited by 25 | Viewed by 4783

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 [...] Read more.

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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15 pages, 445 KiB

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

by Eleni Fitsiou, Gregoria Mitropoulou, Katerina Spyridopoulou, Angeliki Tiptiri-Kourpeti, Manolis Vamvakias, Haido Bardouki, Mihalis Ι. Panayiotidis, Alex Galanis, Yiannis Kourkoutas, Katerina Chlichlia and Aglaia Pappa

Molecules 2016, 21(8), 1069; https://doi.org/10.3390/molecules21081069 - 16 Aug 2016

Cited by 111 | Viewed by 15799

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), [...] Read more.

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), Pimpinella anisum (anise) and Fortunella margarita (kumquat). GC/MS analyses revealed that the major components in the essential oil fractions, were carvone (85.4%) in spearmint, methyl chavicol (74.9%) in sweet basil, trans-anethole (88.1%) in anise, and limonene (93.8%) in kumquat. We further explored their biological potential by studying their antimicrobial, antioxidant and antiproliferative activities. Only the essential oils from spearmint and sweet basil demonstrated cytotoxicity against common foodborne bacteria, while all preparations were active against the fungi Saccharomyces cerevisiae and Aspergillus niger. Antioxidant evaluation by DPPH and ABTS radical scavenging activity assays revealed a variable degree of antioxidant potency. Finally, their antiproliferative potential was tested against a panel of human cancer cell lines and evaluated by using the sulforhodamine B (SRB) assay. All essential oil preparations exhibited a variable degree of antiproliferative activity, depending on the cancer model used, with the most potent one being sweet basil against an in vitro model of human colon carcinoma. Full article

(This article belongs to the Collection Bioactive Compounds)

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35 pages, 11017 KiB

Open AccessArticle

Extended N-Arylsulfonylindoles as 5-HT₆ Receptor Antagonists: Design, Synthesis & Biological Evaluation

by Gonzalo Vera, Carlos F. Lagos, Sebastián Almendras, Dan Hebel, Francisco Flores, Gissella Valle-Corvalán, C. David Pessoa-Mahana, Jaime Mella-Raipán, Rodrigo Montecinos and Gonzalo Recabarren-Gajardo

Molecules 2016, 21(8), 1070; https://doi.org/10.3390/molecules21081070 - 16 Aug 2016

Cited by 14 | Viewed by 6537

Abstract

Based on a known pharmacophore model for 5-HT₆ receptor antagonists, a series of novel extended derivatives of the N-arylsulfonyindole scaffold were designed and identified as a new class of 5-HT₆ receptor modulators. Eight of the compounds exhibited moderate to high [...] Read more.

Based on a known pharmacophore model for 5-HT₆ receptor antagonists, a series of novel extended derivatives of the N-arylsulfonyindole scaffold were designed and identified as a new class of 5-HT₆ receptor modulators. Eight of the compounds exhibited moderate to high binding affinities and displayed antagonist profile in 5-HT₆ receptor functional assays. Compounds 2-(4-(2-methoxyphenyl)piperazin-1-yl)-1-(1-tosyl-1H-indol-3-yl)ethanol (4b), 1-(1-(4-iodophenylsulfonyl)-1H-indol-3-yl)-2-(4-(2-methoxyphenyl)piperazin-1-yl)ethanol (4g) and 2-(4-(2-methoxyphenyl)piperazin-1-yl)-1-(1-(naphthalen-1-ylsulfonyl)-1H-indol-3-yl)ethanol (4j) showed the best binding affinity (4b pK_i = 7.87; 4g pK_i = 7.73; 4j pK_i = 7.83). Additionally, compound 4j was identified as a highly potent antagonist (IC₅₀ = 32 nM) in calcium mobilisation functional assay. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 3027 KiB

Open AccessArticle

Neuroprotective Effects of Methyl 3,4-Dihydroxybenzoate against TBHP-Induced Oxidative Damage in SH-SY5Y Cells

by Liang Cai, Li-Fang Wang, Jun-Ping Pan, Xiang-Nan Mi, Zheng Zhang, Hai-Ju Geng, Jia-Hui Wang, Song-Hui Hu, Wei Zhang, Qin Gao, Wu-Tian Wu and Huan-Min Luo

Molecules 2016, 21(8), 1071; https://doi.org/10.3390/molecules21081071 - 22 Aug 2016

Cited by 29 | Viewed by 9595

Abstract

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations [...] Read more.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butyl hydroperoxide (TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM + 10% FBS for 24 h and pretreated with different concentrations of MDHB or N-acetyl-l-cysteine (NAC) for 4 h prior to the addition of 40 μM TBHP for 24 h. Cell viability was analyzed using the methylthiazolyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rates. The 2′,7′-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells. Full article

(This article belongs to the Special Issue Chemistry and Pharmacology of Modulators of Oxidative Stress)

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19 pages, 1615 KiB

Open AccessArticle

Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines

by Abdou O. Abdelhamid, Ibrahim E. El Sayed, Mohamed Z. Hussein and Mangoud M. Mangoud

Molecules 2016, 21(8), 1072; https://doi.org/10.3390/molecules21081072 - 17 Aug 2016

Cited by 19 | Viewed by 8537

Abstract

A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly [...] Read more.

A novel series of 1,3,4-thiadiazoles, 5-arylazothiazoles and hexahydropyrimido-[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines were synthesized via reaction of hydrazonoyl halides with each of alkyl carbothioates, carbothioamides and 7-thioxo-5,6,7,8-tetrahydropyrimido-[4,5-d]pyrimidine-2,4(1H,3H)-diones in the presence of triethylamine. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their antimicrobial activity against various microorganisms. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 1144 KiB

Open AccessArticle

Aqueous DMSO Mediated Conversion of (2-(Arylsulfonyl)vinyl)iodonium Salts to Aldehydes and Vinyl Chlorides

by Eman Zawia and Wesley J. Moran

Molecules 2016, 21(8), 1073; https://doi.org/10.3390/molecules21081073 - 16 Aug 2016

Cited by 10 | Viewed by 5522

Abstract

Vinyl(aryl)iodonium salts are useful compounds in organic synthesis but they are under-utilized and their chemistry is under-developed. Herein is described the solvolysis of some vinyl(phenyl)iodonium salts, bearing an arylsulfonyl group, in aqueous DMSO leading to aldehyde formation. This unusual process is selective and [...] Read more.

Vinyl(aryl)iodonium salts are useful compounds in organic synthesis but they are under-utilized and their chemistry is under-developed. Herein is described the solvolysis of some vinyl(phenyl)iodonium salts, bearing an arylsulfonyl group, in aqueous DMSO leading to aldehyde formation. This unusual process is selective and operates under ambient conditions. Furthermore, the addition of aqueous HCl and DMSO to these vinyl(aryl)iodonium salts allows their facile conversion to vinyl chlorides. Full article

(This article belongs to the Special Issue Hypervalent Iodine Chemistry)

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9 pages, 997 KiB

Open AccessArticle

Steroidal Saponins from the Rhizomes of Anemarrhena asphodeloides

by Bing-You Yang, Jing Zhang, Yan Liu and Hai-Xue Kuang

Molecules 2016, 21(8), 1075; https://doi.org/10.3390/molecules21081075 - 17 Aug 2016

Cited by 24 | Viewed by 6613

Abstract

Four new steroid saponins 1–4 were isolated from the rhizomes of Anemarrhena asphodeloides (Asparagaceae), as well as four known saponins: anemarsaponin B (5) timosaponin D (6), timosaponin E1 (7) anemarsaponin B II (8). [...] Read more.

Four new steroid saponins 1–4 were isolated from the rhizomes of Anemarrhena asphodeloides (Asparagaceae), as well as four known saponins: anemarsaponin B (5) timosaponin D (6), timosaponin E1 (7) anemarsaponin B II (8). Their structures were established through UV and NMR as well as MS data. All the compounds were evaluated for cytotoxicity against HepG2 and SGC7901 human cancer lines. Compounds 3 and 7 displayed medium antiproliferative activities on HepG2 and SGC7901 cells, with IC₅₀ values of 43.90 and 57.90 μM, respectively. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 1993 KiB

Open AccessArticle

Quantitative Analysis of Psoralea corylifolia Linne and its Neuroprotective and Anti-Neuroinflammatory Effects in HT22 Hippocampal Cells and BV-2 Microglia

by Yu Jin Kim, Hye-Sun Lim, Jun Lee and Soo-Jin Jeong

Molecules 2016, 21(8), 1076; https://doi.org/10.3390/molecules21081076 - 17 Aug 2016

Cited by 50 | Viewed by 7823

Abstract

The seeds of Psoralea corylifolia L. (P. corylifolia), also known as “Bo-Gol-Zhee” in Korea, are used in a traditional herbal medicine for treating various skin diseases. In the present study, we performed quantitative analyses of the seven standard components of P. [...] Read more.

The seeds of Psoralea corylifolia L. (P. corylifolia), also known as “Bo-Gol-Zhee” in Korea, are used in a traditional herbal medicine for treating various skin diseases. In the present study, we performed quantitative analyses of the seven standard components of P. corylifolia: psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol, using high-performance liquid chromatography. We also investigated the neuroprotective and anti-neuroinflammation effects of P. corylifolia and its standard components in the hippocampal cell line HT22 and microglia cell line BV-2. A 70% ethanol extract of P. corylifolia was prepared and the seven standard components were separated using C-18 analytical columns by gradient solvents with acetonitrile and water, and ultraviolet detection at 215, 225 and 275 nm. The analytical method showed high linearity, with a correlation coefficient of ≥0.9999. The amounts of the standard components ranged from 0.74 to 11.71 mg/g. Among the components, bakuchiol (11.71 mg/g) was the most potent phytochemical component of P. corylifolia. Furthermore, we analyzed the inhibitory effects of the components from P. corylifolia to determine the bioactive compound needed to regulate neuronal cell changes. Angelicin, isobavachalcone, and bakuchiol suppressed lipopolysaccharide (LPS)-stimulated nitric oxide production in LPS-treated BV-2 microglia more significantly than did the other components. In HT22 hippocampal cells, neobavaisoflavone and bakuchiol had more potent inhibitory activity against hydrogen peroxide-induced cell death. Taken together of the quantification and efficacy analyses, bakuchiol appeared to be the most potent bioactive phytochemical component of P. corylifolia for the potential treatment of neurodegenerative diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 2992 KiB

Open AccessArticle

Antinociceptive Effect of 3-(2,3-Dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one in Mice Models of Induced Nociception

by Nur Izzati Ismail, Lee Ming-Tatt, Nordin Lajis, Muhammad Nadeem Akhtar, Ahmad Akira, Enoch Kumar Perimal, Daud Ahmad Israf and Mohd Roslan Sulaiman

Molecules 2016, 21(8), 1077; https://doi.org/10.3390/molecules21081077 - 22 Aug 2016

Cited by 17 | Viewed by 6182

Abstract

The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It [...] Read more.

The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 8225 KiB

Open AccessArticle

σ-Bond Electron Delocalization in Oligosilanes as Function of Substitution Pattern, Chain Length, and Spatial Orientation

by Johann Hlina, Filippo Stella, Mohammad Aghazadeh Meshgi, Christoph Marschner and Judith Baumgartner

Molecules 2016, 21(8), 1079; https://doi.org/10.3390/molecules21081079 - 18 Aug 2016

Cited by 13 | Viewed by 6391

Abstract

Polysilanes are known to exhibit the interesting property of σ-bond electron delocalization. By employing optical spectroscopy (UV-vis), it is possible to judge the degree of delocalization and also differentiate parts of the molecules which are conjugated or not. The current study compares oligosilanes [...] Read more.

Polysilanes are known to exhibit the interesting property of σ-bond electron delocalization. By employing optical spectroscopy (UV-vis), it is possible to judge the degree of delocalization and also differentiate parts of the molecules which are conjugated or not. The current study compares oligosilanes of similar chain length but different substitution pattern. The size of the substituents determines the spatial orientation of the main chain and also controls the conformational flexibility. The chemical nature of the substituents affects the orbital energies of the molecules and thus the positions of the absorption bands. Full article

(This article belongs to the Special Issue Advances in Silicon Chemistry)

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12 pages, 6334 KiB

Open AccessArticle

Near-Infrared Emitting PbS Quantum Dots for in Vivo Fluorescence Imaging of the Thrombotic State in Septic Mouse Brain

by Yukio Imamura, Sayumi Yamada, Setsuko Tsuboi, Yuko Nakane, Yoshikazu Tsukasaki, Akihito Komatsuzaki and Takashi Jin

Molecules 2016, 21(8), 1080; https://doi.org/10.3390/molecules21081080 - 18 Aug 2016

Cited by 51 | Viewed by 8190

Abstract

Near-infrared (NIR) fluorescent imaging is a powerful tool for the non-invasive visualization of the inner structure of living organisms. Recently, NIR fluorescence imaging at 1000–1400 nm (second optical window) has been shown to offer better spatial resolution compared with conventional NIR fluorescence imaging [...] Read more.

Near-infrared (NIR) fluorescent imaging is a powerful tool for the non-invasive visualization of the inner structure of living organisms. Recently, NIR fluorescence imaging at 1000–1400 nm (second optical window) has been shown to offer better spatial resolution compared with conventional NIR fluorescence imaging at 700–900 nm (first optical window). Here we report lead sulfide (PbS) quantum dots (QDs) and their use for in vivo NIR fluorescence imaging of cerebral venous thrombosis in septic mice. Highly fluorescent PbS QDs with a 1100 nm emission peak (QD1100) were prepared from lead acetate and hexamethyldisilathiane, and the surface of QD1100 was coated with mercaptoundecanoic acid so as to be soluble in water. NIR fluorescence imaging of the cerebral vessels of living mice was performed after intravascular injection (200–300 μL) of QD1100 (3 μM) from a caudal vein. By detecting the NIR fluorescence of QD1100, we achieved non-invasive NIR fluorescence imaging of cerebral blood vessels through the scalp and skull. We also achieved NIR fluorescence imaging of cerebral venous thrombosis in septic mice induced by the administration of lipopolysaccharide (LPS). From the NIR fluorescence imaging, we found that the number of thrombi in septic mice was significantly increased by the administration of LPS. The formation of thrombi in cerebral blood vessels in septic mice was confirmed by enzyme-linked immunosorbent assay (ELISA). We also found that the number of thrombi significantly decreased after the administration of heparin, an inhibitor of blood coagulation. These results show that NIR fluorescence imaging with QD1100 is useful for the evaluation of the pathological state of cerebral blood vessels in septic mice. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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12 pages, 3074 KiB

Open AccessArticle

Emission Enhancement and Intermittency in Polycrystalline Organolead Halide Perovskite Films

by Cheng Li, Yu Zhong, Carlos Andres Melo Luna, Thomas Unger, Konstantin Deichsel, Anna Gräser, Jürgen Köhler, Anna Köhler, Richard Hildner and Sven Huettner

Molecules 2016, 21(8), 1081; https://doi.org/10.3390/molecules21081081 - 18 Aug 2016

Cited by 37 | Viewed by 9929

Abstract

Inorganic-organic halide organometal perovskites have demonstrated very promising performance for opto-electronic applications, such as solar cells, light-emitting diodes, lasers, single-photon sources, etc. However, the little knowledge on the underlying photophysics, especially on a microscopic scale, hampers the further improvement of devices based on [...] Read more.

Inorganic-organic halide organometal perovskites have demonstrated very promising performance for opto-electronic applications, such as solar cells, light-emitting diodes, lasers, single-photon sources, etc. However, the little knowledge on the underlying photophysics, especially on a microscopic scale, hampers the further improvement of devices based on this material. In this communication, correlated conventional photoluminescence (PL) characterization and wide-field PL imaging as a function of time are employed to investigate the spatially- and temporally-resolved PL in CH₃NH₃PbI_3−xCl_x perovskite films. Along with a continuous increase of the PL intensity during light soaking, we also observe PL blinking or PL intermittency behavior in individual grains of these films. Combined with significant suppression of PL blinking in perovskite films coated with a phenyl-C61-butyric acid methyl ester (PCBM) layer, it suggests that this PL intermittency is attributed to Auger recombination induced by photoionized defects/traps or mobile ions within grains. These defects/traps are detrimental for light conversion and can be effectively passivated by the PCBM layer. This finding paves the way to provide a guideline on the further improvement of perovskite opto-electronic devices. Full article

(This article belongs to the Special Issue Perovskite Solar Cells)

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15 pages, 2256 KiB

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Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells

by Yangkang So, Seung Young Lee, Ah-Reum Han, Jin-Baek Kim, Hye Gwang Jeong and Chang Hyun Jin

Molecules 2016, 21(8), 1083; https://doi.org/10.3390/molecules21081083 - 18 Aug 2016

Cited by 33 | Viewed by 7785

Abstract

In this study, we investigated the anti-inflammatory effect of rosmarinic acid methyl ester (RAME) isolated from a mutant cultivar of Perilla frutescens (L.) Britton. We found that RAME inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with an IC₅₀ of 14.25 µM, in [...] Read more.

In this study, we investigated the anti-inflammatory effect of rosmarinic acid methyl ester (RAME) isolated from a mutant cultivar of Perilla frutescens (L.) Britton. We found that RAME inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with an IC₅₀ of 14.25 µM, in RAW 264.7 cells. RAME inhibited the LPS-induced expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, interferon-β, and inducible nitric oxide synthase (iNOS). Moreover, RAME suppressed the activation of nuclear factor kappa B. These results suggest that the downregulation of iNOS expression by RAME was due to myeloid differentiation primary response gene 88 (MyD88)-dependent and -independent pathways. Furthermore, RAME induced the expression of heme oxygenase-1 (HO-1) through activation of nuclear factor-erythroid 2-related factor 2. Treatment with tin protoporphyrin, an inhibitor of HO-1, reversed the RAME-induced suppression of NO production. Taken together, RAME isolated from P. frutescens inhibited NO production in LPS-treated RAW 264.7 cells through simultaneous induction of HO-1 and inhibition of MyD88-dependent and -independent pathways. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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12 pages, 5509 KiB

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Antibacterial Activity and Membrane-Disruptive Mechanism of 3-p-trans-Coumaroyl-2-hydroxyquinic Acid, a Novel Phenolic Compound from Pine Needles of Cedrus deodara, against Staphylococcus aureus

by Yanping Wu, Jinrong Bai, Kai Zhong, Yina Huang, Huayi Qi, Yan Jiang and Hong Gao

Molecules 2016, 21(8), 1084; https://doi.org/10.3390/molecules21081084 - 18 Aug 2016

Cited by 144 | Viewed by 8612

Abstract

Recently, we reported that a novel phenolic compound isolated from Cedrus deodara, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA), exhibits a potent antioxidant activity. The present study aimed to evaluate the antibacterial activity of CHQA against eleven food-borne pathogens and to elucidate [...] Read more.

Recently, we reported that a novel phenolic compound isolated from Cedrus deodara, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA), exhibits a potent antioxidant activity. The present study aimed to evaluate the antibacterial activity of CHQA against eleven food-borne pathogens and to elucidate its mechanism of action against Staphylococcus aureus. The results from minimum inhibitory concentration (MIC) determinations showed that CHQA exhibited moderate inhibitory effects on all of the tested pathogens with MIC values ranging from 2.5–10 mg/mL. Membrane potential measurements and flow cytometric analysis demonstrated that CHQA damaged the cytoplasmic membrane of S. aureus, causing a significant membrane hyperpolarization with a loss of membrane integrity. Moreover, CHQA induced an increase in membrane fluidity and conformational changes in membrane protein of S. aureus, suggesting that CHQA probably acts on the cell membrane by interactions with membrane lipid and protein. Transmission electron microscopic observations further confirmed that CHQA disrupted the cell membrane of S. aureus and caused severe morphological changes, which even led to leakage of intracellular constituents. These findings indicated that CHQA could have the potential to serve as a natural antibacterial agent to control and prevent the growth of pathogens in food and in food-processing environments. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 1338 KiB

Open AccessArticle

Immunomodulatory and Antioxidant Effects of Polysaccharides from Gynostemma pentaphyllum Makino in Immunosuppressed Mice

by Xiaoya Shang, Yu Chao, Yuan Zhang, Chengyuan Lu, Chunlan Xu and Weining Niu

Molecules 2016, 21(8), 1085; https://doi.org/10.3390/molecules21081085 - 19 Aug 2016

Cited by 48 | Viewed by 7949

Abstract

The immunomodulatory and antioxidant activities of crude polysaccharides extracted from Gynostemma pentaphyllum Makino (GPMPP) were investigated. GPMPP was composed of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.39:3.76:1.00:1.64:4.98:5.88. In vivo studies showed GPMPP significantly increased the spleen and [...] Read more.

The immunomodulatory and antioxidant activities of crude polysaccharides extracted from Gynostemma pentaphyllum Makino (GPMPP) were investigated. GPMPP was composed of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.39:3.76:1.00:1.64:4.98:5.88. In vivo studies showed GPMPP significantly increased the spleen and thymus indices, activated the macrophage phagocytosis and NK cells, and exhibited activity on none or Con A/LPS-stimulated splenocytes in a dose-dependent manner in C57BL/6 mice. Moreover, GPMPP elevated CD4⁺ T lymphocyte counts as well as the CD4⁺/CD8⁺ ratio dose-dependently, and it increased IL-2 level in the sera and spleen of Cy-immunosuppressed mice. Furthermore, GPMPP significantly increased the SOD, GSH-Px, T-AOC, GSH and CAT level, and decreased the MDA level. The results showed that GPMPP might play an important role in prevention of oxidative damage in immunological system. These findings indicate GPMPP has immunomodulatory activity in vivo and seems to be an effective natural immunomodulatory agent. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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13 pages, 2335 KiB

Open AccessArticle

Porphyromonas gingivalis Lipopolysaccharide Induced Proliferation and Activation of Natural Killer Cells in Vivo

by Yuhua Wang, Wei Zhang, Li Xu and Jun-O Jin

Molecules 2016, 21(8), 1086; https://doi.org/10.3390/molecules21081086 - 19 Aug 2016

Cited by 15 | Viewed by 8829

Abstract

Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) promoted different innate immune activation than that promoted by Escherichia coli (E. coli) LPS. In this study, we examined the effect of P. gingivalis LPS on the proliferation and activation of natural killer [...] Read more.

Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) promoted different innate immune activation than that promoted by Escherichia coli (E. coli) LPS. In this study, we examined the effect of P. gingivalis LPS on the proliferation and activation of natural killer (NK) cells in vivo and compared that function with that of E. coli LPS. Administration of P. gingivalis LPS to C57BL/6 mice induced stronger proliferation of NK cells in the spleen and submandibular lymph nodes (sLNs) and increased the number of circulating NK cells in blood compared to those treated with E. coli LPS. However, P. gingivalis LPS did not induce interferon-gamma (IFN-γ) production and CD69 expression in the spleen and sLN NK cells in vivo, and this was attributed to the minimal activation of the spleen and sLN dendritic cells (DCs), including low levels of co-stimulatory molecule expression and pro-inflammatory cytokine production. Furthermore, P. gingivalis LPS-treated NK cells showed less cytotoxic activity against Yac-1 target cells than E. coli LPS-treated NK cells. Hence, these data demonstrated that P. gingivalis LPS promoted limited activation of spleen and sLN NK cells in vivo, and this may play a role in the chronic inflammatory state observed in periodontal disease. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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17 pages, 3174 KiB

Open AccessArticle

Assessment of Phenolic Compounds and Anti-Inflammatory Activity of Ethyl Acetate Phase of Anacardium occidentale L. Bark

by Marina Suênia de Araújo Vilar, Graziene Lopes De Souza, Daniela De Araújo Vilar, Jacqueline Alves Leite, Fernanda Nervo Raffin, José Maria Barbosa-Filho, Fernando Henrique Andrade Nogueira, Sandra Rodrigues-Mascarenhas and Túlio Flávio Accioly de Lima Moura

Molecules 2016, 21(8), 1087; https://doi.org/10.3390/molecules21081087 - 19 Aug 2016

Cited by 37 | Viewed by 6972

Abstract

The bark of A. occidentale L. is rich in tannins. Studies have described various biological activities of the plant, including antimicrobial, antioxidant, antiulcerogenic and antiinflammatory actions. The objective of this study was to assess the activity of the ethyl acetate phase (EtOAc) of [...] Read more.

The bark of A. occidentale L. is rich in tannins. Studies have described various biological activities of the plant, including antimicrobial, antioxidant, antiulcerogenic and antiinflammatory actions. The objective of this study was to assess the activity of the ethyl acetate phase (EtOAc) of A. occidentale on acute inflammation and to identify and quantify its phenolic compounds by HPLC. The method was validated and shown to be linear, precise and accurate for catechin, epicatechin, epigallocatechin and gallic acid. Swiss albino mice (Mus musculus) were treated with saline, Carrageenan (2.5%), Indomethacin (10 mg/kg), Bradykinin (6 nmol) and Prostaglandine E2 (5 µg) at different concentrations of EtOAc - A. occidentale (12.5; 25; 50; and 100 mg/kg/weight p.o.) for the paw edema test. Challenge was performed with carrageenan (500 µg/mL i.p.) for the doses 50 and 100 mg/kg of EtOAc. Levels of cytokines IL-1, TNF-α, IL-6 and IL-10 were also measured. All EtOAc - A. occidentale concentrations reduced the edema. At 50 and 100 mg/kg, an anti-inflammatory response of the EtOAc was observed. Carrageenan stimulus produced a neutrophil count of 28.6% while 50 and 100 mg/kg of the phase reduced this to 14.5% and 9.1%, respectively. The EtOAc extract reduced levels of IL-1 and TNF-α. These results suggest that the EtOAc plays a modulatory role in the inflammatory response. The chromatographic method can be used for the analysis of the phenolic compounds of the EtOAc phase. Full article

(This article belongs to the Special Issue Natural Products and Inflammation)

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15 pages, 3764 KiB

Open AccessArticle

Copper Ion Attenuated the Antiproliferative Activity of Di-2-pyridylhydrazone Dithiocarbamate Derivative; However, There Was a Lack of Correlation between ROS Generation and Antiproliferative Activity

by Tingting Wang, Yun Fu, Tengfei Huang, Youxun Liu, Meihao Wu, Yanbin Yuan, Shaoshan Li and Changzheng Li

Molecules 2016, 21(8), 1088; https://doi.org/10.3390/molecules21081088 - 20 Aug 2016

Cited by 20 | Viewed by 6983

Abstract

The use of chelators for cancer treatment has been an alternative option. Dithiocarbamates have recently attracted considerable attention owning to their diverse biological activities; thus, the preparation of new dithiocarbamate derivatives with improved antitumor activity and selectivity as well as probing the underlying [...] Read more.

The use of chelators for cancer treatment has been an alternative option. Dithiocarbamates have recently attracted considerable attention owning to their diverse biological activities; thus, the preparation of new dithiocarbamate derivatives with improved antitumor activity and selectivity as well as probing the underlying molecular mechanism are required. In this study, di-2-pyridylhydrazone dithiocarbamate S-propionic acid (DpdtpA) and its copper complex were prepared and characterized, and its antiproliferative activity was evaluated. The proliferation inhibition assay showed that DpdtpA exhibited excellent antiproliferative effect in hepatocellular carcinoma (IC₅₀ = 1.3 ± 0.3 μM for HepG2, and 2.5 ± 0.6 μM for Bel-7402). However, in the presence of copper ion, the antiproliferative activity of DpdtpA was dramatically attenuated (20–30 fold) owing to the formation of copper chelate. A preliminarily mechanistic study revealed that reactive oxygen species (ROS) generation mediated the antiproliferative activity of DpdtpA, and accordingly induced apoptosis, DNA cleavage, and autophagy. Surprisingly, the cytotoxicity of DpdtpA copper complex (DpdtpA–Cu) was also involved in ROS generation; however, a paradoxical relation between cellular ROS level and cytotoxicity was observed. Further investigation indicated that DpdtpA could induce cell cycle arrest at the S phase; however, DpdtpA–Cu lacked this effect, which explained the difference in their antiproliferative activity. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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10 pages, 565 KiB

Open AccessArticle

Five New Biphenanthrenes from Cremastra appendiculata

by Liang Liu, Jun Li, Ke-Wu Zeng, Yong Jiang and Peng-Fei Tu

Molecules 2016, 21(8), 1089; https://doi.org/10.3390/molecules21081089 - 19 Aug 2016

Cited by 34 | Viewed by 6100

Abstract

Five new biphenanthrenes, cremaphenanthrenes A–E (1–5), along with six known ones, were isolated from the ethanolic extract of the tubers of Cremastra appendiculata (D. Don) Makino (Orchidaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. All [...] Read more.

Five new biphenanthrenes, cremaphenanthrenes A–E (1–5), along with six known ones, were isolated from the ethanolic extract of the tubers of Cremastra appendiculata (D. Don) Makino (Orchidaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. All the compounds obtained were tested in vitro for cytotoxic activities against colon (HCT-116), cervix (Hela), and breast (MDA-MB-231) cancer cell lines. They all showed moderate or weak cytotoxicities to the above cancer cell lines. Full article

(This article belongs to the Special Issue Natural Products and Chronic Diseases)

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11 pages, 1055 KiB

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Protein Tyrosine Phosphatase 1B Inhibitors from the Stems of Akebia quinata

by Jin-Pyo An, Thi Kim Quy Ha, Jinwoong Kim, Tae Oh Cho and Won Keun Oh

Molecules 2016, 21(8), 1091; https://doi.org/10.3390/molecules21081091 - 19 Aug 2016

Cited by 31 | Viewed by 7250

Abstract

PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B [...] Read more.

PTP1B deficiency in mouse mammary tumor virus (MMTV)-NeuNT transgenic mice inhibited the onset of MMTV-NeuNT-evoked breast cancer, while its overexpression was observed in breast cancer. Thus, PTP1B inhibitors are considered chemopreventative agents for breast cancer. As part of our program to find PTP1B inhibitors, one new diterpene glycoside (1) and 13 known compounds (2–14) were isolated from the methanol extract of the stems of Akebia quinata. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR and MS. Compounds 2, 3, 6, 8 and 11 showed significant inhibitory effects on the PTP1B enzyme, with IC₅₀ values ranging from 4.08 ± 1.09 to 21.80 ± 4.74 μM. PTP1B inhibitors also had concentration-dependent cytotoxic effects on breast cancer cell lines, such as MCF7, MDA-MB-231 and tamoxifen-resistant MCF7 (MCF7/TAMR) (IC₅₀ values ranging from 0.84 ± 0.04 to 7.91 ± 0.39 μM). These results indicate that compounds 6 and 8 from Akebia quinata may be lead compounds acting as anti-breast cancer agents. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 2205 KiB

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Comprehensive Quantitative Analysis of SQ Injection Using Multiple Chromatographic Technologies

by Siu-Leung Chau, Zhi-Bing Huang, Yan-Gang Song, Rui-Qi Yue, Alan Ho, Chao-Zhan Lin, Wen-Hua Huang and Quan-Bin Han

Molecules 2016, 21(8), 1092; https://doi.org/10.3390/molecules21081092 - 19 Aug 2016

Cited by 8 | Viewed by 7927

Abstract

Quality control of Chinese medicine injections remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling injections, Shenqi Fuzheng (SQ) injection (SQI), via a full component quantitative [...] Read more.

Quality control of Chinese medicine injections remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling injections, Shenqi Fuzheng (SQ) injection (SQI), via a full component quantitative analysis. A total of 15 representative small molecular components of SQI were simultaneously determined using ultra-high performance liquid chromatography (UHPLC) coupled with quadrupole tandem time-of-flight mass spectrometry (Q-TOF-MS); saccharide composition of SQI was also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on an amino column before and after acid hydrolysis. The existence of polysaccharides was also examined on a gel permeation chromatography column. The method was well validated in terms of linearity, sensitivity, precision, accuracy and stability, and was successfully applied to analyze 13 SQI samples. The results demonstrate that up to 94.69% (w/w) of this injection product are quantitatively determined, in which small molecules and monosaccharide/sucrose account for 0.18%–0.21%, and 53.49%–58.2%, respectively. The quantitative information contributes to accumulating scientific evidence to better understand the therapy efficacy and safety of complex Chinese medicine injections. Full article

(This article belongs to the Collection Herbal Medicine Research)

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12 pages, 5157 KiB

Open AccessArticle

Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model

by Yisong Qian, Xuzhen Tang, Teng Guan, Yunman Li and Hongbin Sun

Molecules 2016, 21(8), 1093; https://doi.org/10.3390/molecules21081093 - 19 Aug 2016

Cited by 27 | Viewed by 6973

Abstract

Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the [...] Read more.

Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining, neuronal damage was assessed by Haematoxylin Eosin (H&E) staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP) was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke. Full article

(This article belongs to the Collection Neuroprotection Mediated by Natural Products and Their Chemical Derivatives)

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14 pages, 7932 KiB

Open AccessArticle

Compositions, Formation Mechanism, and Neuroprotective Effect of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang

by Chenze Zhang, Rui Zhao, Wenqiang Yan, Hui Wang, Menglu Jia, Nailiang Zhu, Yindi Zhu, Yuzhong Zhang, Penglong Wang and Haimin Lei

Molecules 2016, 21(8), 1094; https://doi.org/10.3390/molecules21081094 - 19 Aug 2016

Cited by 53 | Viewed by 7038

Abstract

Compounds in the form of precipitation (CFP) are universally formed during the decocting of Chinese prescriptions, such as Huang-Lian-Jie-Du-Tang (HLJDT). The formation rate of HLJDT CFP even reached 2.63% ± 0.20%. The identification by liquid chromatography mass spectrometry (LC-MSⁿ) proved that [...] Read more.

Compounds in the form of precipitation (CFP) are universally formed during the decocting of Chinese prescriptions, such as Huang-Lian-Jie-Du-Tang (HLJDT). The formation rate of HLJDT CFP even reached 2.63% ± 0.20%. The identification by liquid chromatography mass spectrometry (LC-MSⁿ) proved that the main chemical substances of HLJDT CFP are baicalin and berberine, which is coincident with the theory that the CFP might derive from interaction between acidic and basic compounds. To investigate the formation mechanism of HLJDT CFP, baicalin and berberine were selected to synthesize a simulated precipitation and then the baicalin–berberine complex was obtained. Results indicated that the melting point of the complex interposed between baicalin and berberine, and the UV absorption, was different from the mother material. In addition, ¹H-NMR integral and high-resolution mass spectroscopy (HR-MS) can validate that the binding ratio was 1:1. Compared with baicalin, the chemical shifts of H and C on glucuronide had undergone significant changes by ¹H-, ¹³C-NMR, which proved that electron transfer occurred between the carboxylic proton and the lone pair of electrons on the N atom. Both HLJDT CFP and the baicalin–berberine complex showed protective effects against cobalt chloride-induced neurotoxicity in differentiated PC12 cells. It is a novel idea, studying the material foundation of CFP in Chinese prescriptions. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1506 KiB

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Beneficial Effects of Trillium govanianum Rhizomes in Pain and Inflammation

by Shafiq Ur Rahman, Achyut Adhikari, Muhammad Ismail, Muhammad Raza Shah, Muhammad Khurram, Muhammad Shahid, Farman Ali, Abdul Haseeb, Fazal Akbar and Marcello Iriti

Molecules 2016, 21(8), 1095; https://doi.org/10.3390/molecules21081095 - 20 Aug 2016

Cited by 31 | Viewed by 9048

Abstract

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity [...] Read more.

Trillium govanianum rhizome is used as an analgesic and anti-inflammatory remedy in traditional medicine in northern Pakistan. In an attempt to establish its medicinal value, the present research evaluated the analgesic and anti-inflammatory potential of T. govanianum. The in vivo anti-inflammatory activity of extract and fractions was investigated in the carrageenan induced paw edema assay. The in vitro suppression of oxidative burst of extract, fractions and isolated compounds was assessed through luminol-enhanced chemiluminescence assay. The in vivo analgesic activity was assayed in chemical and thermal induced nociceptive pain models. The crude methanol extract and its solvent fractions showed anti-inflammatory and analgesic responses, exhibited by significant amelioration of paw edema and relieve of the tonic visceral chemical and acute phasic thermal nociception. In the oxidative burst assay, based on IC₅₀, the crude methanol extract and n-butanol soluble fraction produced a significant inhibition, followed by chloroform and hexane soluble fractions as compared to ibuprofen. Similarly, the isolated compounds pennogenin and borassoside E exhibited significant level of oxidative burst suppressive activity. The in vivo anti-inflammatory and analgesic activities as well as the in vitro inhibition of oxidative burst validated the traditional use of T. govanianum rhizomes as a phytotherapeutic remedy for both inflammatory conditions and pain. The observed activities might be attributed to the presence of steroids and steroid-based compounds. Therefore, the rhizomes of this plant species could serve as potential novel source of compounds effective for alleviating pain and inflammation. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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17 pages, 3016 KiB

Open AccessArticle

Optimization of the Ultrasonic-Assisted Extraction of Bioactive Flavonoids from Ampelopsis grossedentata and Subsequent Separation and Purification of Two Flavonoid Aglycones by High-Speed Counter-Current Chromatography

by Hongbing Zhang, Guoyong Xie, Mei Tian, Qian Pu and Minjian Qin

Molecules 2016, 21(8), 1096; https://doi.org/10.3390/molecules21081096 - 20 Aug 2016

Cited by 36 | Viewed by 6808

Abstract

The fermented leaf of Ampelopsis grossedentata has been used as a beverage and folk medicine called “vine tea” in the southern region of China. In this paper, the optimum extraction conditions for the maximum recovery amounts of total flavonoids (TF), dihydromyricetin (DMY), myricitrin [...] Read more.

The fermented leaf of Ampelopsis grossedentata has been used as a beverage and folk medicine called “vine tea” in the southern region of China. In this paper, the optimum extraction conditions for the maximum recovery amounts of total flavonoids (TF), dihydromyricetin (DMY), myricitrin (MYG) and myricetin (MY) from natural Ampelopsis grossedentata leaves subjected to ultrasonic-assisted extraction (UAE) were determined and optimized by using response surface methodology. The method was employed by the Box–Behnken design (BBD) and Derringer’s desirability function using methanol concentration, extraction time, liquid/solid ratio as factors and the contents of TF, DMY, MYG and MY as responses. The obtained optimum UAE conditions were as follows: a solvent of 80.87% methanol, an extraction time of 31.98 min and a liquid/solid ratio of 41.64:1 mL/g. Through analysis of the response surface, it implied that methanol concentration and the liquid/solid ratio had significant effects on TF, DMY, MYG and MY yields, whereas extraction time had relatively little effects. The established extraction and analytical methods were successfully applied to determine the contents of the total flavonoids and three individual flavonoids in 10 batches of the leaf samples of A. grossedentata from three counties in Fujian Province, China. The results suggested the variability in the quality of A. grossedentata leaves from different origins. In addition, high purities of dihydromyricetin and myricetin were simultaneously separated and purified from the extract subjected to optimized UAE, by high-speed counter-current chromatography using a solvent system of N-hexane–ethyl acetate–methanol–water (1:3:2:4; v/v/v/v). In a single operation, 200 mg of the extract were separated to yield 86.46 mg of dihydromyricetin and 3.61 mg of myricetin with the purity of 95.03% and 99.21%, respectively. The results would be beneficial for further exploiting the herbal products and controlling the quality of the herb and its derived products. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues)

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13 pages, 978 KiB

Open AccessArticle

Four New Dicaffeoylquinic Acid Derivatives from Glasswort (Salicornia herbacea L.) and Their Antioxidative Activity

by Jeong-Yong Cho, Jin Young Kim, Yu Geon Lee, Hyoung Jae Lee, Hyun Jeong Shim, Ji Hye Lee, Seon-Jae Kim, Kyung-Sik Ham and Jae-Hak Moon

Molecules 2016, 21(8), 1097; https://doi.org/10.3390/molecules21081097 - 20 Aug 2016

Cited by 37 | Viewed by 8351

Abstract

Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5-dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, [...] Read more.

Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5-dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, and 3,5-di-dihydrocaffeoylquinic acid methyl ester. Their chemical structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy (LC-ESI-MS). In addition, the presence of dicaffeoylquinic acid derivatives in this plant was reconfirmed by LC-ESI-MS/MS analysis. The isolated compounds strongly scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited cholesteryl ester hydroperoxide formation during rat blood plasma oxidation induced by copper ions. These results indicate that the caffeoylquinic acid derivatives may partially contribute to the antioxidative effect of S. herbacea. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 408 KiB

Open AccessArticle

Effect of the Production of Dried Fruits and Juice from Chokeberry (Aronia melanocarpa L.) on the Content and Antioxidative Activity of Bioactive Compounds

by Jan Oszmiański and Sabina Lachowicz

Molecules 2016, 21(8), 1098; https://doi.org/10.3390/molecules21081098 - 22 Aug 2016

Cited by 104 | Viewed by 10005

Abstract

The aim of this study was to evaluate the production of dried fruits and juices from chokeberry as potential sources of bioactive compounds with beneficial effects on human health. Dry powders and juices from chokeberry were analyzed for the contents of sugars with [...] Read more.

The aim of this study was to evaluate the production of dried fruits and juices from chokeberry as potential sources of bioactive compounds with beneficial effects on human health. Dry powders and juices from chokeberry were analyzed for the contents of sugars with high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC-ELSD method), and the antioxidant capacity was analyzed by the FRAP (ferric-reducing ability of plasma) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) tests. Polyphenols were identified by high performance liquid chromatography (HPLC) coupled with a tandem mass spectrometer and a photodiode-array detector (LC-PDA-ESI-MS/MS), and their quantitative analysis was carried out by UPLC-MS/MS (using a Q/TOF detector and a PDA detector). A total of 27 polyphenolic compounds was identified in chokeberry products, including 7 anthocyanins, 11 flavonols, 5 phenolic acids, 3 flavan-3-ols and 1 flavanone. Three anthocyanin derivatives were reported for the first time from chokeberry fruit. A higher activity of the bioactive compounds was determined in dried fruit pomace and in juice obtained from crushed fruits than in those from the whole fruits. In addition, the pomace was found to be a better material for the production of dry powders, compared to chokeberry fruits. Full article

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14 pages, 4915 KiB

Open AccessArticle

Effect of Mono- and Poly-CH/P Exchange(s) on the Aromaticity of the Tropylium Ion

by Ankita Puri and Raakhi Gupta

Molecules 2016, 21(8), 1099; https://doi.org/10.3390/molecules21081099 - 20 Aug 2016

Cited by 4 | Viewed by 8512

Abstract

In view of the fact that the phosphorus atom in its low co-ordination state (coordination numbers 1 and 2) has been termed as the carbon copy, there have been attempts to investigate, theoretically as well as experimentally, the effect of the exchange(s) of [...] Read more.

In view of the fact that the phosphorus atom in its low co-ordination state (coordination numbers 1 and 2) has been termed as the carbon copy, there have been attempts to investigate, theoretically as well as experimentally, the effect of the exchange(s) of CH- moiety with phosphorus atom(s) (CH/P) on the structural and other aspects of the classical carbocyclic and heterocyclic systems. Tropylium ion is a well-known non-benzenoid aromatic system and has been studied extensively for its aromatic character. We have now investigated the effect of mono- and poly-CH/P exchange(s) on the aromaticity of the tropylium ion. For this purpose, the parameters based on the geometry and magnetic properties, namely bond equalization, aromatic stabilization energies (ASE), Nucleus-Independent Chemical Shift (NICS) values, (NICS(0), NICS(1), NICS(1)_zz), proton nucleus magnetic resonance (¹H-NMR) chemical shifts, magnetic susceptibility exaltation and magnetic anisotropic values of mono-, di-, tri- and tetra-phosphatropylium ions have been determined at the Density Functional Theory (DFT) (B3LYP/6-31+G(d)) level. Geometry optimization reveals bond length equalization. ASEs range from −46.3 kcal/mol to −6.2 kcal/mol in mono- and diphospha-analogues which are planar. However, the ions having three and four phosphorus atoms lose planarity and their ASE values approach the values typical for non-aromatic structures. Of the three NICS values, the NICS(1)_zz is consistently negative showing aromatic character of all the systems studied. It is also supported by the magnetic susceptibility exaltations and magnetic anisotropic values. Furthermore, ¹H-NMR chemical shifts also fall in the aromatic region. The conclusion that mono-, di-, tri- and tetra-phosphatropylium ions are aromatic in nature has been further corroborated by determining the energy gap between the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) (HOMO − LUMO gap), which falls in the range, ca. 3 × 10⁻¹⁹–9 × 10⁻¹⁹ J. The systems having more than four phosphorus atoms are not able to sustain their monocyclic structure. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

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12 pages, 1628 KiB

Open AccessArticle

Self-Supported N-Heterocyclic Carbenes and Their Use as Organocatalysts

by Shuang Ma and Patrick H. Toy

Molecules 2016, 21(8), 1100; https://doi.org/10.3390/molecules21081100 - 20 Aug 2016

Cited by 5 | Viewed by 6296

Abstract

The study of N-heterocyclic carbenes (NHCs) as organocatalysts has proliferated in recent years, and they have been found to be useful in a variety of reactions. In an attempt to further expand their utility and to study their recyclability, we designed and [...] Read more.

The study of N-heterocyclic carbenes (NHCs) as organocatalysts has proliferated in recent years, and they have been found to be useful in a variety of reactions. In an attempt to further expand their utility and to study their recyclability, we designed and synthesized a series of self-supported NHCs in which the catalytic carbene groups form part of a densely functionalized polymer backbone, and studied them as organocatalysts. Of the self-Supported NHCs examined, a benzimidazole derived polymer with flexible linkers connecting the catalytic groups was found to be the most efficient organocatalyst in a model benzoin condensation reaction, and thus it was used in a variety of such reactions, including some involving catalyst recycling. Furthermore, it was also used to catalyze a set of redox esterification reactions involving conjugated unsaturated aldehydes. In all of these reactions the catalyst afforded good yield of the desired product and its polymeric nature facilitated product purification. Full article

(This article belongs to the Special Issue Recent Advancements in Polymer-Supported Catalysis)

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10 pages, 1362 KiB

Open AccessArticle

A Novel Insecticidal Peptide SLP1 Produced by Streptomyces laindensis H008 against Lipaphis erysimi

by Lijian Xu, Kangkang Liang, Bensha Duan, Mengdi Yu, Wei Meng, Qinggui Wang and Qiong Yu

Molecules 2016, 21(8), 1101; https://doi.org/10.3390/molecules21081101 - 22 Aug 2016

Cited by 6 | Viewed by 5769

Abstract

Aphids are major insect pests for crops, causing damage by direct feeding and transmission of plant diseases. This paper was completed to discover and characterize a novel insecticidal metabolite against aphids from soil actinobacteria. An insecticidal activity assay was used to screen 180 [...] Read more.

Aphids are major insect pests for crops, causing damage by direct feeding and transmission of plant diseases. This paper was completed to discover and characterize a novel insecticidal metabolite against aphids from soil actinobacteria. An insecticidal activity assay was used to screen 180 bacterial strains from soil samples against mustard aphid, Lipaphis erysimi. The bacterial strain H008 showed the strongest activity, and it was identified by the phylogenetic analysis of the 16S rRNA gene and physiological traits as a novel species of genus Streptomyces (named S. laindensis H008). With the bioassay-guided method, the insecticidal extract from S. laindensis H008 was subjected to chromatographic separations. Finally, a novel insecticidal peptide was purified from Streptomyces laindensis H008 against L. erysimi, and it was determined to be S-E-P-A-Q-I-V-I-V-D-G-V-D-Y-W by TOF-MS and amino acid analysis. Full article

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11 pages, 3406 KiB

Open AccessArticle

Furfural Production from d-Xylose and Xylan by Using Stable Nafion NR50 and NaCl in a Microwave-Assisted Biphasic Reaction

by Sarah Le Guenic, David Gergela, Claire Ceballos, Frederic Delbecq and Christophe Len

Molecules 2016, 21(8), 1102; https://doi.org/10.3390/molecules21081102 - 22 Aug 2016

Cited by 58 | Viewed by 7653

Abstract

Pentose dehydration and direct transformation of xylan into furfural were performed in a water-cyclopentyl methyl ether (CPME) biphasic system under microwave irradiation. Heated up between 170 and 190 °C in the presence of Nafion NR50 and NaCl, d-xylose, l-arabinose and xylan [...] Read more.

Pentose dehydration and direct transformation of xylan into furfural were performed in a water-cyclopentyl methyl ether (CPME) biphasic system under microwave irradiation. Heated up between 170 and 190 °C in the presence of Nafion NR50 and NaCl, d-xylose, l-arabinose and xylan gave furfural with maximum yields of 80%, 42% and 55%, respectively. The influence of temperature and reaction time on the reaction kinetics was discussed. This study was also completed by the survey of different reactant ratios, such as organic layer-water or catalyst-inorganic salt ratios. The exchange between proton and cation induced by an excess of NaCl was monitored, and a synergetic effect between the remaining protons and the released HCl was also discovered. Full article

(This article belongs to the Special Issue Catalysis Applied to Biomass—Toward Sustainable Processes and Chemicals)

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15 pages, 3051 KiB

Open AccessArticle

Gold Nanocluster Decorated Polypeptide/DNA Complexes for NIR Light and Redox Dual-Responsive Gene Transfection

by Qi Lei, Jing-Jing Hu, Lei Rong, Han Cheng, Yun-Xia Sun and Xian-Zheng Zhang

Molecules 2016, 21(8), 1103; https://doi.org/10.3390/molecules21081103 - 20 Aug 2016

Cited by 16 | Viewed by 7358

Abstract

Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could [...] Read more.

Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR-irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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17 pages, 3948 KiB

Open AccessArticle

Ribosome Inactivating Proteins from Rosaceae

by Chenjing Shang, Pierre Rougé and Els J. M. Van Damme

Molecules 2016, 21(8), 1105; https://doi.org/10.3390/molecules21081105 - 22 Aug 2016

Cited by 17 | Viewed by 5830

Abstract

Ribosome-inactivating proteins (RIPs) are widespread among higher plants of different taxonomic orders. In this study, we report on the RIP sequences found in the genome/transcriptome of several important Rosaceae species, including many economically important edible fruits such as apple, pear, peach, apricot, and [...] Read more.

Ribosome-inactivating proteins (RIPs) are widespread among higher plants of different taxonomic orders. In this study, we report on the RIP sequences found in the genome/transcriptome of several important Rosaceae species, including many economically important edible fruits such as apple, pear, peach, apricot, and strawberry. All RIP domains from Rosaceae share high sequence similarity with conserved residues in the catalytic site and the carbohydrate binding sites. The genomes of Malus domestica and Pyrus communis contain both type 1 and type 2 RIP sequences, whereas for Prunus mume, Prunus persica, Pyrus bretschneideri, and Pyrus communis a complex set of type 1 RIP sequences was retrieved. Heterologous expression and purification of the type 1 as well as the type 2 RIP from apple allowed to characterize the biological activity of the proteins. Both RIPs from Malus domestica can inhibit protein synthesis. Furthermore, molecular modelling suggests that RIPs from Rosaceae possess three-dimensional structures that are highly similar to the model proteins and can bind to RIP substrates. Screening of the recombinant type 2 RIP from apple on a glycan array revealed that this type 2 RIP interacts with terminal sialic acid residues. Our data suggest that the RIPs from Rosaceae are biologically active proteins. Full article

(This article belongs to the Special Issue Ribosome-Inactivating Proteins--Commemorative Issue in Honor of Professor Fiorenzo Stirpe)

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Review

Jump to: Editorial, Research

14 pages, 777 KiB

Open AccessReview

Capsaicin: From Plants to a Cancer-Suppressing Agent

by Angela M. Chapa-Oliver and Laura Mejía-Teniente

Molecules 2016, 21(8), 931; https://doi.org/10.3390/molecules21080931 - 27 Jul 2016

Cited by 220 | Viewed by 23773

Abstract

Capsaicinoids are plant secondary metabolites, capsaicin being the principal responsible for the pungency of chili peppers. It is biosynthesized through two pathways involved in phenylpropanoid and fatty acid metabolism. Plant capsaicin concentration is mainly affected by genetic, environmental and crop management factors. However, [...] Read more.

Capsaicinoids are plant secondary metabolites, capsaicin being the principal responsible for the pungency of chili peppers. It is biosynthesized through two pathways involved in phenylpropanoid and fatty acid metabolism. Plant capsaicin concentration is mainly affected by genetic, environmental and crop management factors. However, its synthesis can be enhanced by the use of elicitors. Capsaicin is employed as food additive and in pharmaceutical applications. Additionally, it has been found that capsaicin can act as a cancer preventive agent and shows wide applications against various types of cancer. This review is an approach in contextualizing the use of controlled stress on the plant to increase the content of capsaicin, highlighting its synthesis and its potential use as anticancer agent. Full article

(This article belongs to the Special Issue Capsaicin)

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54 pages, 23154 KiB

Open AccessReview

1,3-Dipolar Cycloaddition Reactions of Azomethine Ylides with Carbonyl Dipolarophiles Yielding Oxazolidine Derivatives

by Adam G. Meyer and John H. Ryan

Molecules 2016, 21(8), 935; https://doi.org/10.3390/molecules21080935 - 23 Jul 2016

Cited by 81 | Viewed by 17908

Abstract

We provide a comprehensive account of the 1,3-dipolar cycloaddition reactions of azomethine ylides with carbonyl dipolarophiles. Many different azomethine ylides have been studied, including stabilized and non-stabilized ylides. Of the carbonyl dipolarophiles, aldehydes including formaldehyde are the most studied, although there are now [...] Read more.

We provide a comprehensive account of the 1,3-dipolar cycloaddition reactions of azomethine ylides with carbonyl dipolarophiles. Many different azomethine ylides have been studied, including stabilized and non-stabilized ylides. Of the carbonyl dipolarophiles, aldehydes including formaldehyde are the most studied, although there are now examples of cycloadditions with ketones, ketenes and carboxyl systems, in particular isatoic anhydrides and phthalic anhydrides. Intramolecular cycloadditions with esters can also occur under certain circumstances. The oxazolidine cycloadducts undergo a range of reactions triggered by the ring-opening of the oxazolidine ring system. Full article

(This article belongs to the Special Issue Pericyclic Reactions)

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28 pages, 1308 KiB

Open AccessReview

Harnessing the Therapeutic Potential of Capsaicin and Its Analogues in Pain and Other Diseases

by Shaherin Basith, Minghua Cui, Sunhye Hong and Sun Choi

Molecules 2016, 21(8), 966; https://doi.org/10.3390/molecules21080966 - 23 Jul 2016

Cited by 167 | Viewed by 26179

Abstract

Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and [...] Read more.

Capsaicin is the most predominant and naturally occurring alkamide found in Capsicum fruits. Since its discovery in the 19th century, the therapeutic roles of capsaicin have been well characterized. The potential applications of capsaicin range from food flavorings to therapeutics. Indeed, capsaicin and few of its analogues have featured in clinical research covered by more than a thousand patents. Previous records suggest pleiotropic pharmacological activities of capsaicin such as an analgesic, anti-obesity, anti-pruritic, anti-inflammatory, anti-apoptotic, anti-cancer, anti-oxidant, and neuro-protective functions. Moreover, emerging data indicate its clinical significance in treating vascular-related diseases, metabolic syndrome, and gastro-protective effects. The dearth of potent drugs for management of such disorders necessitates the urge for further research into the pharmacological aspects of capsaicin. This review summarizes the historical background, source, structure and analogues of capsaicin, and capsaicin-triggered TRPV1 signaling and desensitization processes. In particular, we will focus on the therapeutic roles of capsaicin and its analogues in both normal and pathophysiological conditions. Full article

(This article belongs to the Special Issue Capsaicin)

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32 pages, 1033 KiB

Open AccessReview

Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks

by João P. Monteiro, Marco G. Alves, Pedro F. Oliveira and Branca M. Silva

Molecules 2016, 21(8), 974; https://doi.org/10.3390/molecules21080974 - 27 Jul 2016

Cited by 127 | Viewed by 19750

Abstract

Methylxanthines are a group of phytochemicals derived from the purine base xanthine and obtained from plant secondary metabolism. They are unobtrusively included in daily diet in common products as coffee, tea, energetic drinks, or chocolate. Caffeine is by far the most studied methylxanthine [...] Read more.

Methylxanthines are a group of phytochemicals derived from the purine base xanthine and obtained from plant secondary metabolism. They are unobtrusively included in daily diet in common products as coffee, tea, energetic drinks, or chocolate. Caffeine is by far the most studied methylxanthine either in animal or epidemiologic studies. Theophylline and theobromine are other relevant methylxanthines also commonly available in the aforementioned sources. There are many disseminated myths about methylxanthines but there is increased scientific knowledge to discuss all the controversy and promise shown by these intriguing phytochemicals. In fact, many beneficial physiologic outcomes have been suggested for methylxanthines in areas as important and diverse as neurodegenerative and respiratory diseases, diabetes or cancer. However, there have always been toxicity concerns with methylxanthine (over)consumption and pharmacologic applications. Herein, we explore the structure-bioactivity relationships to bring light those enumerated effects. The potential shown by methylxanthines in such a wide range of conditions should substantiate many other scientific endeavors that may highlight their adequacy as adjuvant therapy agents and may contribute to the advent of functional foods. Newly designed targeted molecules based on methylxanthine structure may originate more specific and effective outcomes. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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20 pages, 986 KiB

Open AccessReview

Coffee Consumption and Oxidative Stress: A Review of Human Intervention Studies

by Daniela Martini, Cristian Del Bo’, Michele Tassotti, Patrizia Riso, Daniele Del Rio, Furio Brighenti and Marisa Porrini

Molecules 2016, 21(8), 979; https://doi.org/10.3390/molecules21080979 - 28 Jul 2016

Cited by 135 | Viewed by 25593

Abstract

Research on the potential protective effects of coffee and its bioactives (caffeine, chlorogenic acids and diterpenes) against oxidative stress and related chronic disease risk has been increasing in the last years. The present review summarizes the main findings on the effect of coffee [...] Read more.

Research on the potential protective effects of coffee and its bioactives (caffeine, chlorogenic acids and diterpenes) against oxidative stress and related chronic disease risk has been increasing in the last years. The present review summarizes the main findings on the effect of coffee consumption on protection against lipid, protein and DNA damage, as well as on the modulation of antioxidant capacity and antioxidant enzymes in human studies. Twenty-six dietary intervention studies (involving acute and chronic coffee intake) have been considered. Overall, the results suggest that coffee consumption can increase glutathione levels and improve protection against DNA damage, especially following regular/repeated intake. On the contrary, the effects of coffee on plasma antioxidant capacity and antioxidant enzymes, as well as on protein and lipid damage, are unclear following both acute and chronic exposure. The high heterogeneity in terms of type of coffee, doses and duration of the studies, the lack of information on coffee and/or brew bioactive composition, as well as the choice of biomarkers and the methods used for their evaluation, may partially explain the variability observed among findings. More robust and well-controlled intervention studies are necessary for a thorough understanding of the effect of coffee on oxidative stress markers in humans. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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16 pages, 1621 KiB

Open AccessReview

Native Mass Spectrometry in Fragment-Based Drug Discovery

by Liliana Pedro and Ronald J. Quinn

Molecules 2016, 21(8), 984; https://doi.org/10.3390/molecules21080984 - 28 Jul 2016

Cited by 57 | Viewed by 12115

Abstract

The advent of native mass spectrometry (MS) in 1990 led to the development of new mass spectrometry instrumentation and methodologies for the analysis of noncovalent protein–ligand complexes. Native MS has matured to become a fast, simple, highly sensitive and automatable technique with well-established [...] Read more.

The advent of native mass spectrometry (MS) in 1990 led to the development of new mass spectrometry instrumentation and methodologies for the analysis of noncovalent protein–ligand complexes. Native MS has matured to become a fast, simple, highly sensitive and automatable technique with well-established utility for fragment-based drug discovery (FBDD). Native MS has the capability to directly detect weak ligand binding to proteins, to determine stoichiometry, relative or absolute binding affinities and specificities. Native MS can be used to delineate ligand-binding sites, to elucidate mechanisms of cooperativity and to study the thermodynamics of binding. This review highlights key attributes of native MS for FBDD campaigns. Full article

(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)

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23 pages, 12785 KiB

Open AccessReview

Recent Advances in Metal-Free Quinoline Synthesis

by Ginelle A. Ramann and Bryan J. Cowen

Molecules 2016, 21(8), 986; https://doi.org/10.3390/molecules21080986 - 29 Jul 2016

Cited by 142 | Viewed by 24355

Abstract

The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. [...] Read more.

The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner–Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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25 pages, 1087 KiB

Open AccessReview

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

by Zhenzhen Xue and Bin Yang

Molecules 2016, 21(8), 991; https://doi.org/10.3390/molecules21080991 - 29 Jul 2016

Cited by 111 | Viewed by 13242

Abstract

Phenylethanoid glycosides (PhGs) are widely distributed in traditional Chinese medicines as well as in other medicinal plants, and they were characterized by a phenethyl alcohol (C₆-C₂) moiety attached to a β-glucopyranose/β-allopyranose via a glycosidic bond. The outstanding activity of [...] Read more.

Phenylethanoid glycosides (PhGs) are widely distributed in traditional Chinese medicines as well as in other medicinal plants, and they were characterized by a phenethyl alcohol (C₆-C₂) moiety attached to a β-glucopyranose/β-allopyranose via a glycosidic bond. The outstanding activity of PhGs in diverse diseases proves their importance in medicinal chemistry research. This review summarizes new findings on PhGs over the past 10 years, concerning the new structures, their bioactivities, including neuroprotective, anti-inflammatory, antioxidant, antibacterial and antivirus, cytotoxic, immunomodulatory, and enzyme inhibitory effects, and pharmacokinetic properties. Full article

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24 pages, 6357 KiB

Open AccessReview

Computational Approaches to Toll-Like Receptor 4 Modulation

by Jean-Marc Billod, Alessandra Lacetera, Joan Guzmán-Caldentey and Sonsoles Martín-Santamaría

Molecules 2016, 21(8), 994; https://doi.org/10.3390/molecules21080994 - 30 Jul 2016

Cited by 71 | Viewed by 12466

Abstract

Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram-negative bacteria, activating the innate immune response. Some TLR4 modulators are undergoing [...] Read more.

Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram-negative bacteria, activating the innate immune response. Some TLR4 modulators are undergoing preclinical and clinical evaluation for the treatment of sepsis, inflammatory diseases, cancer and rheumatoid arthritis. Since the relatively recent elucidation of the X-ray crystallographic structure of the extracellular domain of TLR4, research around this fascinating receptor has risen to a new level, and thus, new perspectives have been opened. In particular, diverse computational techniques have been applied to decipher some of the basis at the atomic level regarding the mechanism of functioning and the ligand recognition processes involving the TLR4/MD-2 system at the atomic level. This review summarizes the reported molecular modeling and computational studies that have recently provided insights into the mechanism regulating the activation/inactivation of the TLR4/MD-2 system receptor and the key interactions modulating the molecular recognition process by agonist and antagonist ligands. These studies have contributed to the design and the discovery of novel small molecules with promising activity as TLR4 modulators. Full article

(This article belongs to the Special Issue Computational Design: A New Approach to Drug and Molecular Discovery)

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21 pages, 1920 KiB

Open AccessReview

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery

by Pakama Mahlumba, Yahya E. Choonara, Pradeep Kumar, Lisa C. Du Toit and Viness Pillay

Molecules 2016, 21(8), 1002; https://doi.org/10.3390/molecules21081002 - 30 Jul 2016

Cited by 38 | Viewed by 8803

Abstract

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of [...] Read more.

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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16 pages, 4272 KiB

Open AccessReview

Microfluidic Devices in Advanced Caenorhabditis elegans Research

by Muniesh Muthaiyan Shanmugam and Tuhin Subhra Santra

Molecules 2016, 21(8), 1006; https://doi.org/10.3390/molecules21081006 - 2 Aug 2016

Cited by 26 | Viewed by 8862

Abstract

The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, [...] Read more.

The study of model organisms is very important in view of their potential for application to human therapeutic uses. One such model organism is the nematode worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with human disease genes and, therefore, studies on C. elegans can be translated to human, as well as, C. elegans can be used in the study of different types of parasitic worms that infect other living organisms. In the past decade, many efforts have been undertaken to establish interdisciplinary research collaborations between biologists, physicists and engineers in order to develop microfluidic devices to study the biology of C. elegans. Microfluidic devices with the power to manipulate and detect bio-samples, regents or biomolecules in micro-scale environments can well fulfill the requirement to handle worms under proper laboratory conditions, thereby significantly increasing research productivity and knowledge. The recent development of different kinds of microfluidic devices with ultra-high throughput platforms has enabled researchers to carry out worm population studies. Microfluidic devices primarily comprises of chambers, channels and valves, wherein worms can be cultured, immobilized, imaged, etc. Microfluidic devices have been adapted to study various worm behaviors, including that deepen our understanding of neuromuscular connectivity and functions. This review will provide a clear account of the vital involvement of microfluidic devices in worm biology. Full article

(This article belongs to the Special Issue Micro/Nano Fluidics and Bio-MEMS)

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18 pages, 2670 KiB

Open AccessReview

Hydrolytic Metallo-Nanozymes: From Micelles and Vesicles to Gold Nanoparticles

by Fabrizio Mancin, Leonard J. Prins, Paolo Pengo, Lucia Pasquato, Paolo Tecilla and Paolo Scrimin

Molecules 2016, 21(8), 1014; https://doi.org/10.3390/molecules21081014 - 4 Aug 2016

Cited by 54 | Viewed by 10014

Abstract

Although the term nanozymes was coined by us in 2004 to highlight the enzyme-like properties of gold nanoparticles passivated with a monolayer of Zn(II)-complexes in the cleavage of phosphate diesters, systems resembling those metallo-nanoparticles, like micelles and vesicles, have been the subject of [...] Read more.

Although the term nanozymes was coined by us in 2004 to highlight the enzyme-like properties of gold nanoparticles passivated with a monolayer of Zn(II)-complexes in the cleavage of phosphate diesters, systems resembling those metallo-nanoparticles, like micelles and vesicles, have been the subject of investigation since the mid-eighties of the last century. This paper reviews what has been done in the field and compares the different nanosystems highlighting the source of catalysis and frequent misconceptions found in the literature. Full article

(This article belongs to the Special Issue Nanozymes and Beyond)

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47 pages, 13225 KiB

Open AccessReview

Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives

by Mohsine Driowya, Aziza Saber, Hamid Marzag, Luc Demange, Khalid Bougrin and Rachid Benhida

Molecules 2016, 21(8), 1032; https://doi.org/10.3390/molecules21081032 - 9 Aug 2016

Cited by 37 | Viewed by 10721

Abstract

This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. [...] Read more.

This review describes the recent advances in the microwave-assisted synthesis of 7-membered and larger heterocyclic compounds. Several types of reaction for the cyclization step are discussed: Ring Closing Metathesis (RCM), Heck and Sonogashira reactions, Suzuki-Miyaura cross-coupling, dipolar cycloadditions, multi-component reactions (Ugi, Passerini), etc. Green syntheses and solvent-free procedures have been introduced whenever possible. The syntheses discussed herein have been selected to illustrate the huge potential of microwave in the synthesis of highly functionalized molecules with potential therapeutic applications, in high yields, enhanced reaction rates and increased chemoselectivity, compared to conventional methods. More than 100 references from the recent literature are listed in this review. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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19 pages, 3436 KiB

Open AccessReview

Synthesis of Hydroxymethylenebisphosphonic Acid Derivatives in Different Solvents

by Dávid Illés Nagy, Alajos Grün, Sándor Garadnay, István Greiner and György Keglevich

Molecules 2016, 21(8), 1046; https://doi.org/10.3390/molecules21081046 - 11 Aug 2016

Cited by 24 | Viewed by 7724

Abstract

The syntheses of hydroxymethylenebisphosphonic acid derivatives (dronic acid derivatives) starting from the corresponding substituted acetic acids and P-reagents, mainly phosphorus trichloride and phosphorous acid are surveyed according to the solvents applied. The nature of the solvent is a critical point due to the [...] Read more.

The syntheses of hydroxymethylenebisphosphonic acid derivatives (dronic acid derivatives) starting from the corresponding substituted acetic acids and P-reagents, mainly phosphorus trichloride and phosphorous acid are surveyed according to the solvents applied. The nature of the solvent is a critical point due to the heterogeneity of the reaction mixtures. This review sheds light on the optimum choice and ratio of the P-reactants, and on the optimum conditions. Full article

(This article belongs to the Special Issue Recent Advances in Organophosphorus Chemistry)

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24 pages, 1844 KiB

Open AccessReview

Plant Resources, ¹³C-NMR Spectral Characteristic and Pharmacological Activities of Dammarane-Type Triterpenoids

by Jingya Ruan, Chang Zheng, Lu Qu, Yanxia Liu, Lifeng Han, Haiyang Yu, Yi Zhang and Tao Wang

Molecules 2016, 21(8), 1047; https://doi.org/10.3390/molecules21081047 - 12 Aug 2016

Cited by 21 | Viewed by 12336

Abstract

Dammarane-type triterpenoids (DTT) widely distribute in various medicinal plants. They have generated a great amount of interest in the field of new drug research and development. Generally, DTT are the main bioactive ingredients abundant in Araliaceae plants, such as Panax ginseng, P. [...] Read more.

Dammarane-type triterpenoids (DTT) widely distribute in various medicinal plants. They have generated a great amount of interest in the field of new drug research and development. Generally, DTT are the main bioactive ingredients abundant in Araliaceae plants, such as Panax ginseng, P. japonicas, P. notoginseng, and P. quinquefolium. Aside from Araliaceae, DTT also distribute in other families, including Betulaceae, Cucurbitaceae, Meliaceae, Rhamnaceae, and Scrophulariaceae. Until now, about 136 species belonging to 46 families have been reported to contain DTT. In this article, the genus classifications of plant sources of the botanicals that contain DTT are reviewed, with particular focus on the NMR spectral features and pharmacological activities based on literature reports, which may be benefit for the development of new drugs or food additives. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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34 pages, 4152 KiB

Open AccessReview

Parasitic Mistletoes of the Genera Scurrula and Viscum: From Bench to Bedside

by Ya Chee Lim, Rajan Rajabalaya, Shirley Huan Fang Lee, Kushan U. Tennakoon, Quang-Vuong Le, Adi Idris, Ihsan N. Zulkipli, Natasha Keasberry and Sheba R. David

Molecules 2016, 21(8), 1048; https://doi.org/10.3390/molecules21081048 - 17 Aug 2016

Cited by 34 | Viewed by 11767

Abstract

The mistletoes, stem hemiparasites of Asia and Europe, have been used as medicinal herbs for many years and possess sophisticated systems to obtain nutrients from their host plants. Although knowledge about ethnomedicinal uses of mistletoes is prevalent in Asia, systematic scientific study of [...] Read more.

The mistletoes, stem hemiparasites of Asia and Europe, have been used as medicinal herbs for many years and possess sophisticated systems to obtain nutrients from their host plants. Although knowledge about ethnomedicinal uses of mistletoes is prevalent in Asia, systematic scientific study of these plants is still lacking, unlike its European counterparts. This review aims to evaluate the literature on Scurrula and Viscum mistletoes. Both mistletoes were found to have anticancer, antimicrobial, antioxidant and antihypertensive properties. Plants from the genus Scurrula were found to inhibit cancer growth due to presence of phytoconstituents such as quercetin and fatty acid chains. Similar to plants from the genus Viscum, Scurrula also possesses TNFα activity to strengthen the immune system to combat cancer. In line with its anticancer activity, both mistletoes are rich in antioxidants that confer protection against cancer as well as neurodegeneration. Extracts from plants of both genera showed evidence of vasodilation and thus, antihypertensive effects. Other therapeutic effects such as weight loss, postpartum and gastrointestinal healing from different plants of the genus Scurrula are documented. As the therapeutic effects of plants from Scurrula are still in exploration stage, there is currently no known clinical trial on these plants. However, there are few on-going clinical trials for Viscum album that demonstrate the functionalities of these mistletoes. Future work required for exploring the benefits of these plants and ways to develop both parasitic plants as a source of pharmacological drug are explained in this article. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 5261 KiB

Open AccessReview

Bioactive Thiazine and Benzothiazine Derivatives: Green Synthesis Methods and Their Medicinal Importance

by Syed Lal Badshah and Abdul Naeem

Molecules 2016, 21(8), 1054; https://doi.org/10.3390/molecules21081054 - 15 Aug 2016

Cited by 92 | Viewed by 15397

Abstract

Thiazines are a group of heterocyclic organic compounds that are still largely unexplored for their pharmacological activities. There are different available methods for the synthesis of thiazine derivatives in the literature. In this review, we discuss available methods of thiazine preparation through green [...] Read more.

Thiazines are a group of heterocyclic organic compounds that are still largely unexplored for their pharmacological activities. There are different available methods for the synthesis of thiazine derivatives in the literature. In this review, we discuss available methods of thiazine preparation through green synthesis methods. Beside their synthesis, many thiazine derivatives are biologically active and play an important role in the treatment of various diseases and show promising results of varying degrees, where they act as antibacterial, antifungal, antitumor, antimalarial, antineoplastic, antiviral, anti-inflammatory, analgesic and anticancer agents and thus they represent an interesting class of heterocyclic medicinal compounds worthy of further exploration. Full article

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32 pages, 4323 KiB

Open AccessReview

The Role of Natural Polyphenols in the Prevention and Treatment of Cervical Cancer—An Overview

by Marius Alexandru Moga, Oana Gabriela Dimienescu, Cristian Andrei Arvatescu, Aurel Mironescu, Laura Dracea and Liana Ples

Molecules 2016, 21(8), 1055; https://doi.org/10.3390/molecules21081055 - 17 Aug 2016

Cited by 88 | Viewed by 13035

Abstract

Cervical cancer represents the second leading cause of death for women worldwide. The importance of the diet and its impact on specific types of neoplasia has been highlighted, focusing again interest in the analysis of dietary phytochemicals. Polyphenols have shown a wide range [...] Read more.

Cervical cancer represents the second leading cause of death for women worldwide. The importance of the diet and its impact on specific types of neoplasia has been highlighted, focusing again interest in the analysis of dietary phytochemicals. Polyphenols have shown a wide range of cellular effects: they may prevent carcinogens from reaching the targeted sites, support detoxification of reactive molecules, improve the elimination of transformed cells, increase the immune surveillance and the most important factor is that they can influence tumor suppressors and inhibit cellular proliferation, interfering in this way with the steps of carcinogenesis. From the studies reviewed in this paper, it is clear that certain dietary polyphenols hold great potential in the prevention and therapy of cervical cancer, because they interfere in carcinogenesis (in the initiation, development and progression) by modulating the critical processes of cellular proliferation, differentiation, apoptosis, angiogenesis and metastasis. Specifically, polyphenols inhibit the proliferation of HPV cells, through induction of apoptosis, growth arrest, inhibition of DNA synthesis and modulation of signal transduction pathways. The effects of combinations of polyphenols with chemotherapy and radiotherapy used in the treatment of cervical cancer showed results in the resistance of cervical tumor cells to chemo- and radiotherapy, one of the main problems in the treatment of cervical neoplasia that can lead to failure of the treatment because of the decreased efficiency of the therapy. Full article

(This article belongs to the Special Issue New Frontiers on the Metabolism, Bioavailability and Health Effects of Phenolic Compounds)

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16 pages, 962 KiB

Open AccessReview

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

by Prasad L. Polavarapu

Molecules 2016, 21(8), 1056; https://doi.org/10.3390/molecules21081056 - 12 Aug 2016

Cited by 40 | Viewed by 7737

Abstract

Chiroptical spectroscopy has emerged as a promising tool for the determination of absolute configurations and predominant conformations of chiral molecules in academic laboratories. This promise has led to the adaption of chiroptical spectroscopic methods as valuable tools in chiral drug discovery research programs [...] Read more.

Chiroptical spectroscopy has emerged as a promising tool for the determination of absolute configurations and predominant conformations of chiral molecules in academic laboratories. This promise has led to the adaption of chiroptical spectroscopic methods as valuable tools in chiral drug discovery research programs of the pharmaceutical industry. Most major pharmaceutical companies have invested in in-house chiroptical spectroscopy applications and reported successful outcomes. In the context of continuously increasing applications of chiroptical spectroscopy for chiral molecular structure determination, a review of recent developments and applications for chiral drugs is presented in this manuscript. Full article

(This article belongs to the Special Issue Chiral Drugs)

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20 pages, 528 KiB

Open AccessReview

Treatment Modalities for Acne

by Lizelle Fox, Candice Csongradi, Marique Aucamp, Jeanetta Du Plessis and Minja Gerber

Molecules 2016, 21(8), 1063; https://doi.org/10.3390/molecules21081063 - 13 Aug 2016

Cited by 215 | Viewed by 69552

Abstract

Acne is a common inflammatory skin disease which affects the pilosebaceous units of the skin. It can have severe psychological effects and can leave the patient with severe skin scarring. There are four well-recognized pathological factors responsible for acne which is also the [...] Read more.

Acne is a common inflammatory skin disease which affects the pilosebaceous units of the skin. It can have severe psychological effects and can leave the patient with severe skin scarring. There are four well-recognized pathological factors responsible for acne which is also the target for acne therapy. In this review, different treatment options are discussed, including topical (i.e., retinoids, and antibiotics) and systemic (i.e., retinoids, antibiotics, and hormonal) treatments. Since the general public has been showing an increasing interest in more natural and generally safer treatment options, the use of complementary and alternative medicines (CAM) for treating acne was also discussed. The use of physical therapies such as comedone extraction, cryoslush therapy, cryotherapy, electrocauterization, intralesional corticosteroids and optical treatments are also mentioned. Acne has been extensively researched with regards to the disease mechanism as well as treatment options. However, due to the increasing resistance of Propionibacterium acnes towards the available antibiotics, there is a need for new treatment methods. Additionally, the lack of necessary evidence on the efficacy of CAM therapies makes it necessary for researchers to investigate these treatment options further. Full article

(This article belongs to the Special Issue Transdermal Delivery Systems: Current Landscape and Trends)

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38 pages, 1376 KiB

Open AccessReview

Immobilization of Glycoside Hydrolase Families GH1, GH13, and GH70: State of the Art and Perspectives

by Natália G. Graebin, Jéssie Da N. Schöffer, Diandra De Andrades, Plinho F. Hertz, Marco A. Z. Ayub and Rafael C. Rodrigues

Molecules 2016, 21(8), 1074; https://doi.org/10.3390/molecules21081074 - 17 Aug 2016

Cited by 60 | Viewed by 11618

Abstract

Glycoside hydrolases (GH) are enzymes capable to hydrolyze the glycosidic bond between two carbohydrates or even between a carbohydrate and a non-carbohydrate moiety. Because of the increasing interest for industrial applications of these enzymes, the immobilization of GH has become an important development [...] Read more.

Glycoside hydrolases (GH) are enzymes capable to hydrolyze the glycosidic bond between two carbohydrates or even between a carbohydrate and a non-carbohydrate moiety. Because of the increasing interest for industrial applications of these enzymes, the immobilization of GH has become an important development in order to improve its activity, stability, as well as the possibility of its reuse in batch reactions and in continuous processes. In this review, we focus on the broad aspects of immobilization of enzymes from the specific GH families. A brief introduction on methods of enzyme immobilization is presented, discussing some advantages and drawbacks of this technology. We then review the state of the art of enzyme immobilization of families GH1, GH13, and GH70, with special attention on the enzymes β-glucosidase, α-amylase, cyclodextrin glycosyltransferase, and dextransucrase. In each case, the immobilization protocols are evaluated considering their positive and negative aspects. Finally, the perspectives on new immobilization methods are briefly presented. Full article

(This article belongs to the Special Issue Enzyme Immobilization 2016)

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19 pages, 3145 KiB

Open AccessReview

Evaluation of Biosynthetic Pathway and Engineered Biosynthesis of Alkaloids

by Shinji Kishimoto, Michio Sato, Yuta Tsunematsu and Kenji Watanabe

Molecules 2016, 21(8), 1078; https://doi.org/10.3390/molecules21081078 - 18 Aug 2016

Cited by 60 | Viewed by 20275

Abstract

Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants [...] Read more.

Varieties of alkaloids are known to be produced by various organisms, including bacteria, fungi and plants, as secondary metabolites that exhibit useful bioactivities. However, understanding of how those metabolites are biosynthesized still remains limited, because most of these compounds are isolated from plants and at a trace level of production. In this review, we focus on recent efforts in identifying the genes responsible for the biosynthesis of those nitrogen-containing natural products and elucidating the mechanisms involved in the biosynthetic processes. The alkaloids discussed in this review are ditryptophenaline (dimeric diketopiperazine alkaloid), saframycin (tetrahydroisoquinoline alkaloid), strictosidine (monoterpene indole alkaloid), ergotamine (ergot alkaloid) and opiates (benzylisoquinoline and morphinan alkaloid). This review also discusses the engineered biosynthesis of these compounds, primarily through heterologous reconstitution of target biosynthetic pathways in suitable hosts, such as Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. Those heterologous biosynthetic systems can be used to confirm the functions of the isolated genes, economically scale up the production of the alkaloids for commercial distributions and engineer the biosynthetic pathways to produce valuable analogs of the alkaloids. In particular, extensive involvement of oxidation reactions catalyzed by oxidoreductases, such as cytochrome P450s, during the secondary metabolite biosynthesis is discussed in details. Full article

(This article belongs to the Special Issue Diversity of Alkaloids)

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22 pages, 2936 KiB

Open AccessReview

Order, Disorder, and Everything in Between

by Shelly DeForte and Vladimir N. Uversky

Molecules 2016, 21(8), 1090; https://doi.org/10.3390/molecules21081090 - 19 Aug 2016

Cited by 83 | Viewed by 10631

Abstract

In addition to the “traditional” proteins characterized by the unique crystal-like structures needed for unique functions, it is increasingly recognized that many proteins or protein regions (collectively known as intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs)), being biologically active, do [...] Read more.

In addition to the “traditional” proteins characterized by the unique crystal-like structures needed for unique functions, it is increasingly recognized that many proteins or protein regions (collectively known as intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs)), being biologically active, do not have a specific 3D-structure in their unbound states under physiological conditions. There are also subtler categories of disorder, such as conditional (or dormant) disorder and partial disorder. Both the ability of a protein/region to fold into a well-ordered functional unit or to stay intrinsically disordered but functional are encoded in the amino acid sequence. Structurally, IDPs/IDPRs are characterized by high spatiotemporal heterogeneity and exist as dynamic structural ensembles. It is important to remember, however, that although structure and disorder are often treated as binary states, they actually sit on a structural continuum. Full article

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