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257 KiB

Open AccessArticle

MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells

by Qingshan Lv, Mei Yang, Xueting Liu, Lina Zhou, Zhilin Xiao, Xiaobin Chen, Meifang Chen, Xiumei Xie and Jinyue Hu

Molecules 2012, 17(4), 3599-3608; https://doi.org/10.3390/molecules17043599 - 23 Mar 2012

Cited by 11 | Viewed by 8205

Abstract

Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs) with MDP up-regulated the gene expression of type [...] Read more.

Muramyldipeptide (MDP), the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2). Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs) with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF) 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity. Full article

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205 KiB

Open AccessArticle

Effect of the Molecular Mass of Tremella Polysaccharides on Accelerated Recovery from Cyclophosphamide-Induced Leucopenia in Rats

by Rui-Zhi Jiang, Ying Wang, Hao-Ming Luo, Yan-Qiu Cheng, Ying-Hong Chen, Yang Gao and Qi-Pin Gao

Molecules 2012, 17(4), 3609-3617; https://doi.org/10.3390/molecules17043609 - 23 Mar 2012

Cited by 16 | Viewed by 6423

Abstract

The body of tremella were decocted with water, and hydrolyzed with 0.1 mol/L hydrochloric acid for different times, giving tremella polysaccharides with six molecular mass values. The structures of all the tremella polysaccharides had non-reducing terminals of β-D-pyranglucuronide, the backbone was composed of [...] Read more.

The body of tremella were decocted with water, and hydrolyzed with 0.1 mol/L hydrochloric acid for different times, giving tremella polysaccharides with six molecular mass values. The structures of all the tremella polysaccharides had non-reducing terminals of β-D-pyranglucuronide, the backbone was composed of (1→3)-linked β-D-manno-pyranoside, and the side chain composed of (1→6)-linked β-D-xylopyranoside was attached to the C₂ of the backbone mannopyranoside. Immunomodulatory effect studies indicated that tremella polysaccharides increased the counts of leukocytes in the peripheral blood which were significantly lowered by cyclophosphamide, and the lower the molecular mass of the tremella polysaccharide, the better this effect was. Full article

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647 KiB

Open AccessArticle

Response Surface Modeling and Optimization of Accelerated Solvent Extraction of Four Lignans from Fructus Schisandrae

by Li-Chun Zhao, Ying He, Xin Deng, Geng-Liang Yang, Wei Li, Jian Liang and Qian-Li Tang

Molecules 2012, 17(4), 3618-3629; https://doi.org/10.3390/molecules17043618 - 23 Mar 2012

Cited by 50 | Viewed by 9256

Abstract

A new method based on accelerated solvent extraction (ASE) combined with response surface methodology (RSM) modeling and optimization has been developed for the extraction of four lignans in Fructus Schisandrae (the fruits of Schisandra chinensis Baill). The RSM method, based on a three [...] Read more.

A new method based on accelerated solvent extraction (ASE) combined with response surface methodology (RSM) modeling and optimization has been developed for the extraction of four lignans in Fructus Schisandrae (the fruits of Schisandra chinensis Baill). The RSM method, based on a three level and three variable Box-Behnken design (BBD), was employed to obtain the optimal combination of extraction condition. In brief, the lignans schizandrin, schisandrol B, deoxyschizandrin and schisandrin B were optimally extracted with 87% ethanol as extraction solvent, extraction temperature of 160 °C, static extraction time of 10 min, extraction pressure of 1,500 psi, flush volume of 60% and one extraction cycle. The 3D response surface plot and the contour plot derived from the mathematical models were applied to determine the optimal conditions. Under the above conditions, the experimental value of four lignans was 14.72 mg/g, which is in close agreement with the value predicted by the model. Full article

(This article belongs to the Section Natural Products Chemistry)

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330 KiB

Open AccessCommunication

Screening of Anti-Obesity Agent from Herbal Mixtures

by Changhyun Roh, Uhee Jung and Sung-Kee Jo

Molecules 2012, 17(4), 3630-3638; https://doi.org/10.3390/molecules17043630 - 23 Mar 2012

Cited by 23 | Viewed by 12918

Abstract

Globally, one in three of the World’s adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion—Equal to the combined populations of China, Europe and the United [...] Read more.

Globally, one in three of the World’s adults are overweight and one in 10 is obese. By 2015, World Health Organization (WHO) estimates the number of chubby adults will balloon to 2.3 billion—Equal to the combined populations of China, Europe and the United States. The discovery of bioactive compounds from herbs is one possible way to control obesity and to prevent or reduce the risks of developing various obesity-related diseases. In this study, we screened anti-obesity agents such as methyl gallate from the herbal composition known as HemoHIM that actively inhibits lipid formation as evidenced by Oil Red O staining and triglyceride (TG) contents in 3T3-L1 adipocytes, suggesting their use as an anti-obesity agent. Furthermore, the amount of glycerol released from cells into the medium had increased by treatment of methyl gallate in a concentration-dependent manner. The present study suggests that a promising anti-obesity agent like methyl gallate might be of therapeutic interest for the treatment of obesity. Full article

(This article belongs to the Section Natural Products Chemistry)

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652 KiB

Open AccessArticle

Relationship Between Wood Color Parameters Measured by the CIELab System and Extractive and Phenol Content in Acacia mangium and Vochysia guatemalensis from Fast-Growth Plantations

by Róger Moya, Roy Soto Fallas, Pablo Jiménez Bonilla and Carolina Tenorio

Molecules 2012, 17(4), 3639-3652; https://doi.org/10.3390/molecules17043639 - 26 Mar 2012

Cited by 64 | Viewed by 8686

Abstract

The heterogeneity of color distribution between sapwood and heartwood limits the market for wood from fast-growth plantations of tropical species. Wood color is associated with wood extractives contents. This study presents the relationship between wood color parameters measured by the CIELab color system [...] Read more.

The heterogeneity of color distribution between sapwood and heartwood limits the market for wood from fast-growth plantations of tropical species. Wood color is associated with wood extractives contents. This study presents the relationship between wood color parameters measured by the CIELab color system and total amount of extractives and phenolic-type extractives in ethanol-toluene and hot water extracts of wood from two fast-growth plantation species. The results demonstrated that the difference in sapwood and hardwood color in Vochysia guatemalensis and Acacia mangium is caused by lower concentrations of extractives in sapwood of both species. Additionally, variations in total extractive and phenolic content have different effects on the color parameters (L*, a* and b*) of both species studied. In Vochysia guatemalensis wood, parameter L* decreases as total extractive and phenolic content increases; however, parameter a* increases as the content of extractives and phenols increases. In Acacia mangium, the amount of phenols showed no relationship with the color parameters. The ethanol-toluene total extractive content, however, shows a relationship with several color parameters. An increase in the content of total extractives in water and ethanol-toluene increases parameter a*, but decreases parameter L*. Full article

(This article belongs to the Section Natural Products Chemistry)

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273 KiB

Open AccessArticle

In Vitro Antimicrobial and Antioxidant Activities of Ethanolic Extract of Lyophilized Mycelium of Pleurotus ostreatus PQMZ91109

by Emanuel Vamanu

Molecules 2012, 17(4), 3653-3671; https://doi.org/10.3390/molecules17043653 - 26 Mar 2012

Cited by 58 | Viewed by 10039

Abstract

The antioxidant and antimicrobial potential of the ethanolic extract of Pleurotus ostreatus PQMZ91109 mycelium was determined based on inorganic and organic nitrogen sources in the culture medium. The presence of ammonium sulfate resulted in a greater accumulation of bioactive compounds compared with the [...] Read more.

The antioxidant and antimicrobial potential of the ethanolic extract of Pleurotus ostreatus PQMZ91109 mycelium was determined based on inorganic and organic nitrogen sources in the culture medium. The presence of ammonium sulfate resulted in a greater accumulation of bioactive compounds compared with the organic ones. This finding was also confirmed by the low values of the ascertained EC₅₀ and minimum inhibitory concentration (MICs). Among the organic sources, peptone followed by corn extract, led to a more important radical-scavenging activity. The extracts selectively inhibited the tested strains, mainly the two of the genus Candida, at an MIC value of 1.25 mg/mL. The antioxidant potential was evaluated by the inhibition capacity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, β-carotene-linoleic acid, which is the reducing power. In addition, the quantity of the compounds with antioxidant effects confirmed the data obtained, they being present in the extracts. Full article

(This article belongs to the Section Natural Products Chemistry)

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505 KiB

Open AccessArticle

The Feasibility of Enzyme Targeted Activation for Amino Acid/Dipeptide Monoester Prodrugs of Floxuridine; Cathepsin D as a Potential Targeted Enzyme

by Yasuhiro Tsume and Gordon L. Amidon

Molecules 2012, 17(4), 3672-3689; https://doi.org/10.3390/molecules17043672 - 26 Mar 2012

Cited by 14 | Viewed by 7292

Abstract

The improvement of therapeutic efficacy for cancer agents has been a big challenge which includes the increase of tumor selectivity and the reduction of adverse effects at non-tumor sites. In order to achieve those goals, prodrug approaches have been extensively investigated. In this [...] Read more.

The improvement of therapeutic efficacy for cancer agents has been a big challenge which includes the increase of tumor selectivity and the reduction of adverse effects at non-tumor sites. In order to achieve those goals, prodrug approaches have been extensively investigated. In this report, the potential activation enzymes for 5¢-amino acid/dipeptide monoester floxuridine prodrugs in pancreatic cancer cells were selected and the feasibility of enzyme specific activation of prodrugs was evaluated. All prodrugs exhibited the range of 3.0–105.7 min of half life in Capan-2 cell homogenate with the presence and the absence of selective enzyme inhibitors. 5¢-O-L-Phenylalanyl-L-tyrosyl-floxuridine exhibited longer half life only with the presence of pepstatin A. Human cathepsin B and D selectively hydrolized 5¢-O-L-phenylalanyl-L-tyrosylfloxuridine and 5¢-O-L-phenylalanyl-L-glycylfloxuridine compared to the other tested prodrugs. The wide range of growth inhibitory effect by floxuridine prodrugs in Capan-2 cells was observed due to the different affinities of prodrug promoieties to enyzmes. In conclusion, it is feasible to design prodrugs which are activated by specific enzymes. Cathepsin D might be a good candidate as a target enzyme for prodrug activation and 5¢-O-L-phenylalanyl-L-tyrosylfloxuridine may be the best candidate among the tested floxuridine prodrugs. Full article

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746 KiB

Open AccessArticle

Coupling of Nanoporous Chromium, Aluminium-Containing Silicates with an Ionic Liquid for the Transformation of Glucose into 5-(Hydroxymethyl)-2-furaldehyde

by Margarida M. Antunes, Sérgio Lima, Martyn Pillinger and Anabela A. Valente

Molecules 2012, 17(4), 3690-3707; https://doi.org/10.3390/molecules17043690 - 26 Mar 2012

Cited by 6 | Viewed by 8209

Abstract

Micro/mesoporous chromium, aluminium-containing silicates of the type TUD-1 (Al-TUD-1, Cr-TUD-1, CrAl-TUD-1) and zeolite BEA, Cr-BEA, and related composites BEA/TUD-1 and Cr-BEA/TUD-1, were prepared, characterised, and tested as solid acids coupled with the ionic liquid (IL) 1-butyl-3-methylimidazolium chloride ([bmim]Cl) as solvent, in the transformation [...] Read more.

Micro/mesoporous chromium, aluminium-containing silicates of the type TUD-1 (Al-TUD-1, Cr-TUD-1, CrAl-TUD-1) and zeolite BEA, Cr-BEA, and related composites BEA/TUD-1 and Cr-BEA/TUD-1, were prepared, characterised, and tested as solid acids coupled with the ionic liquid (IL) 1-butyl-3-methylimidazolium chloride ([bmim]Cl) as solvent, in the transformation of d-glucose into 5-(hydroxymethyl)-2-furaldehyde (Hmf), at 120 °C. The chromium-containing catalytic systems lead to considerably higher Hmf yields in comparison to the related systems without chromium. The IL is a favourable solvent for this target reaction (in terms of Hmf yields reached) compared to water or dimethylsulfoxide. A detailed study on the stabilities of the nanoporous solid acids in the IL medium is presented. Full article

(This article belongs to the Collection Ionic Liquids)

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314 KiB

Open AccessArticle

Analysis of Organic Volatile Flavor Compounds in Fermented Stinky Tofu Using SPME with Different Fiber Coatings

by Yuping Liu, Zhiwei Miao, Wei Guan and Baoguo Sun

Molecules 2012, 17(4), 3708-3722; https://doi.org/10.3390/molecules17043708 - 26 Mar 2012

Cited by 47 | Viewed by 11143

Abstract

The organic volatile flavor compounds in fermented stinky tofu (FST) were studied using SPME-GC/MS. A total of 39 volatile compounds were identified, including nine esters, seven alcohols, five alkenes, four sulfides, three heterocycles, three carboxylic acids, three ketones, two aldehydes, one phenol, one [...] Read more.

The organic volatile flavor compounds in fermented stinky tofu (FST) were studied using SPME-GC/MS. A total of 39 volatile compounds were identified, including nine esters, seven alcohols, five alkenes, four sulfides, three heterocycles, three carboxylic acids, three ketones, two aldehydes, one phenol, one amine and one ether. These compounds were determined by MS, and conformed by comparison of the retention times of the separated constituents with those of authentic samples and by comparison of retention indexes (RIs) of separated constituents with the RIs reported in the literature. The predominant volatile compound in FST was indole, followed by dimethyl trisulfide, phenol, dimethyl disulfide and dimethyl tetrasulfide. In order to find a better extraction time, the extraction times was optimized for each type of SPME fiber; the results show that the best extraction time for Carboxen/PDMS is 60 min, for PDMS/DVB 30 min, for DVB/CAR/PDMS 60 min and for PDMS 75 min. Of the four fibers used in this work, Carboxen/PDMS is found to be the most suitable to extract the organic volatile flavor compounds in fermented stinky tofu. Full article

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411 KiB

Open AccessArticle

Extracts of Lycoris aurea Induce Apoptosis in Murine Sarcoma S180 Cells

by Na Liao, Mingzhang Ao, Peng Zhang and Longjiang Yu

Molecules 2012, 17(4), 3723-3735; https://doi.org/10.3390/molecules17043723 - 26 Mar 2012

Cited by 24 | Viewed by 7602

Abstract

Lycoris species have been known since long ago as a multi-utility ethnomedicinal herbal in China. It has been reported to exhibit a number of properties such as anticancer, neuroprotective, and antibacterial activities. In the present study, the anticancer efficacy of dichloromethane extracts of [...] Read more.

Lycoris species have been known since long ago as a multi-utility ethnomedicinal herbal in China. It has been reported to exhibit a number of properties such as anticancer, neuroprotective, and antibacterial activities. In the present study, the anticancer efficacy of dichloromethane extracts of Lycoris aurea (DELA), was evaluated both in vivo and in vitro using murine sarcoma 180 cells. To evaluate the effects of DELA on apoptotic cell death, flow cytometry and Western blotting were performed. DELA demonstrated promising inhibition effects on sarcoma 180 cells in vitro and a 53.49% inhibitory rate on cancer cells in vivo. DELA treatment increased thymus indices and spleen indices in vivo, indicating that it reduced tumours, but did not damage the main immune organs. The DELA-evoked increase in apoptotic cell death was accompanied by occurrence of cleaved caspase-3 and decreases in the ratio of Bcl-2/Bax. Further purification and LCMS analysis showed DELA contained homolycorine, 2α-hydroxyoduline, oduline, hippeastrine, 2α-hydroxy-6-O- methyloduline, and 2α-methoxy-6-O-methyloduline. These results indicate that DELA exerted its anticancer effects, at least in part, by inducing cancer cell apoptosis and thus can be considered as a potential candidate agent for treatment of cancer. Full article

(This article belongs to the Section Molecular Diversity)

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1619 KiB

Open AccessArticle

Xanthatin Induces Cell Cycle Arrest at G2/M Checkpoint and Apoptosis via Disrupting NF-κB Pathway in A549 Non-Small-Cell Lung Cancer Cells

by Lei Zhang, Junshan Ruan, Linggeng Yan, Weidong Li, Yu Wu, Li Tao, Feng Zhang, Shizhong Zheng, Aiyun Wang and Yin Lu

Molecules 2012, 17(4), 3736-3750; https://doi.org/10.3390/molecules17043736 - 26 Mar 2012

Cited by 55 | Viewed by 9852

Abstract

Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancer cells, yet little is known about its anticancer mechanism. In this study, we demonstrated that xanthatin had obvious dose-/time-dependent cytotoxicity against the human non-small-cell lung cancer (NSCLC) cell line [...] Read more.

Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancer cells, yet little is known about its anticancer mechanism. In this study, we demonstrated that xanthatin had obvious dose-/time-dependent cytotoxicity against the human non-small-cell lung cancer (NSCLC) cell line A549. Flow cytometry analysis showed xanthatin induced cell cycle arrest at G2/M phase. Xanthatin also had pro-apoptotic effects on A549 cells as evidenced by Hoechst 33258 staining and annexin V-FITC staining. Mechanistic data revealed that xanthatin downregulated Chk1, Chk2, and phosphorylation of CDC2, which contributed to the cell cycle arrest. Xathatin also increased total p53 protein levels, decreased Bcl-2/Bax ratio and expression of the downstream factors procaspase-9 and procaspase-3, which triggered the intrinsic apoptosis pathway. Furthermore, xanthatin blocked phosphorylation of NF-κB (p65) and IκBa, which might also contribute to its pro-apoptotic effects on A549 cells. Xanthatin also inhibited TNFa induced NF-κB (p65) translocation. We conclude that xanthatin displays significant antitumor effects through cell cycle arrest and apoptosis induction in A549 cells. These effects were associated with intrinsic apoptosis pathway and disrupted NF-κB signaling. These results suggested that xanthatin may have therapeutic potential against NSCLC. Full article

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231 KiB

Open AccessArticle

Determination of Rutin in Cigarette Tobacco, Filters, Mainstream Smoke and Burned Ash of Different Branded Cigarettes by High Performance Liquid Chromatography

by Yinshi Sun, Wei Li, Jianhua Wang, Jianjie Bi and Shudong Su

Molecules 2012, 17(4), 3751-3760; https://doi.org/10.3390/molecules17043751 - 26 Mar 2012

Cited by 11 | Viewed by 6688

Abstract

Tobacco consists of at least 3,800 chemical constituents. Among them, rutin is an important polyphenolic secondary metabolite in tobacco, which has positive actions such as antiallergic, anti-inflammatory and vasoactive, antitumor, antibacterial, antiviral and anti-protozoal properties. A high performance liquid chromatography method was used [...] Read more.

Tobacco consists of at least 3,800 chemical constituents. Among them, rutin is an important polyphenolic secondary metabolite in tobacco, which has positive actions such as antiallergic, anti-inflammatory and vasoactive, antitumor, antibacterial, antiviral and anti-protozoal properties. A high performance liquid chromatography method was used to analyze rutin in tobacco and filters, mainstream smoke, and burned ash of ten varieties of cigarettes made in China. The chromatographic analysis was performed on a Hypersil ODS2 column with a gradient elution of acetonitrile and water at a flow rate of 1.0 mL/min. Detection was carried out at 350 nm using a photodiode array detector. The calibration curves for the determination of analytes showed good linearity over the investigated ranges (R² > 0.9998). Precision and reproducibility were evaluated by six replicated analyses, and the R.S.D. values were less than 0.59% and 1.53%. The recoveries were between 98.47 and 100.84%. Under the optimized conditions, namely 45 mL/g of solvent to solid ratio, 30 min of extraction time and 200 W of ultrasound power, the concentrations of rutin in tobacco and filter, mainstream smoke, burned ash of different brands cigarettes were 10.20–63.98, 0.10–0.32, 0.06–0.16 and 0 μg/per cigarette, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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228 KiB

Open AccessArticle

Enhancement of Palmarumycin C₁₂and C₁₃ Production in Liquid Culture of the Endophytic Fungus Berkleasmium sp. Dzf12 by Oligosaccharides from Its Host Plant Dioscorea zingiberensis

by Yan Li, Tijiang Shan, Yan Mou, Peiqin Li, Jianglin Zhao, Wensheng Zhao, Youliang Peng, Ligang Zhou and Chunbang Ding

Molecules 2012, 17(4), 3761-3773; https://doi.org/10.3390/molecules17043761 - 26 Mar 2012

Cited by 13 | Viewed by 6947

Abstract

Three crude oligosaccharides were respectively prepared by acid hydrolysis of three polysaccharides, which were water-extracted polysaccharide (WEP), sodium hydroxide-extracted polysaccharide (SEP) and acid-extracted polysaccharide (AEP) from the rhizomes of Dioscorea zingiberensis. Among the three oligosaccharides, the crude oligosaccharide prepared by acid hydrolysis [...] Read more.

Three crude oligosaccharides were respectively prepared by acid hydrolysis of three polysaccharides, which were water-extracted polysaccharide (WEP), sodium hydroxide-extracted polysaccharide (SEP) and acid-extracted polysaccharide (AEP) from the rhizomes of Dioscorea zingiberensis. Among the three oligosaccharides, the crude oligosaccharide prepared by acid hydrolysis of WEP was found to be the most efficient elicitor to enhance the production of palmarumycins C₁₂ and C₁₃ in liquid culture of endophytic fungus Berkleasmium sp. Dzf12. When OW was applied to the medium at 300 mg/L on day 3 of culture, the maximal yields of palmarumycin C₁₂ (87.96 mg/L) and palmarumycin C₁₃ (422.28 mg/L) were achieved on day 15 of culture, which were 9.83 and 3.24-fold in comparison with those (8.95 and 130.43 mg/L) of control, respectively. The results indicate that addition of the oligosaccharides from the host plant D. zingiberensis should be an effective strategy for enhancing production of palmarumycins C₁₂ and C₁₃ in liquid culture of endophytic fungus Berkleasmium sp. Dzf12. Full article

(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)

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377 KiB

Open AccessArticle

¹⁸F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography

by Jingli Xu, Hang Liu, Guixia Li, Yong He, Rui Ding, Xiao Wang, Man Feng, Shuting Zhang, Yurong Chen, Shilei Li, Mingxia Zhao, Yingruo Li, Chuanmin Qi and Yonghong Dang

Molecules 2012, 17(4), 3774-3793; https://doi.org/10.3390/molecules17043774 - 27 Mar 2012

Cited by 7 | Viewed by 7708

Abstract

We previously reported ¹⁸F-labeled pyrazolo[1,5-a]pyrimidine derivatives: 7-(2-[¹⁸F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([¹⁸F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[¹⁸F]fluoro-4-nitro- benzamide ([¹⁸F]2). Preliminary biodistribution experiments of both compounds showed s slow clearance rate from excretory tissues which warranted further [...] Read more.

We previously reported ¹⁸F-labeled pyrazolo[1,5-a]pyrimidine derivatives: 7-(2-[¹⁸F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([¹⁸F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[¹⁸F]fluoro-4-nitro- benzamide ([¹⁸F]2). Preliminary biodistribution experiments of both compounds showed s slow clearance rate from excretory tissues which warranted further investigation for tumor imaging with PET. Here we modified [¹⁸F]1 and [¹⁸F]2 by introducing polar groups such as ester, hydroxyl and carboxyl and developed three additional ¹⁸F-18 labeled pyrazolo[1,5-a] pyrimidine derivatives: (3-Cyano-7-(2-[¹⁸F]fluoroethylamino)pyrazolo[1,5-a]-pyrimidin-5- yl)methyl acetate ([¹⁸F]3), 7-(2-[¹⁸F]fluoroethylamino)-5-(hydroxymethyl)pyrazolo[1,5-a]- pyrimidine-3-carbonitrile ([¹⁸F]4) and (S)-6-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)-2-(2-[¹⁸F]fluoro-4-nitrobenzamido)hexanoic acid ([¹⁸F]5). The radiolabeled probes were synthesized by nucleophilic substitution of the corresponding tosylate and nitro precursors with¹⁸F-fluoride. In Vitro studies showed higher uptake of [¹⁸F]3 and [¹⁸F]4 than that of [¹⁸F]5 by S180 tumor cells. In Vivo biodistribution studies in mice bearing S180 tumors showed that the uptake of both [¹⁸F]3 and [¹⁸F]4 in tumors displayed an increasing trend while the uptake of [¹⁸F]5 in tumor decreased through the course of the 120 min study. This significant difference in tumor uptake was also found between [¹⁸F]1 and [¹⁸F]2. Thus, we compared the biological behavior of the five tracers and reported the tumor uptake kinetic differences between 2-[¹⁸F]fluoroethylamino- and 2-[¹⁸F]fluoro-4-nitro- benzamidopyrazolo[1,5-a] pyrimidine derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

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205 KiB

Open AccessCommunication

Factors Affecting the Physical Properties of Edible Composite Film Prepared from Zein and Wheat Gluten

by Xingfeng Guo, Yanan Lu, Heping Cui, Xiangxing Jia, Hongchao Bai and Yuxiang Ma

Molecules 2012, 17(4), 3794-3804; https://doi.org/10.3390/molecules17043794 - 27 Mar 2012

Cited by 40 | Viewed by 8000

Abstract

The effects of zein ratio, concentration of glycerol, liquid-solid ratio, ethanol concentration, pH and heat-treatment temperature on the properties of zein/wheat gluten composite films were researched. The results showed that elongation (E) increased with an increase in glycerol or ethanol concentrations, but it [...] Read more.

The effects of zein ratio, concentration of glycerol, liquid-solid ratio, ethanol concentration, pH and heat-treatment temperature on the properties of zein/wheat gluten composite films were researched. The results showed that elongation (E) increased with an increase in glycerol or ethanol concentrations, but it first increased and then decreased with increasing zein/wheat gluten ratio, heat-treatment temperature, pH and the ratio of liquid to solid; Tensile strength (TS) increased with the increase in heat-treatment temperature and pH, and decreased with the increase in glycerol or ethanol concentrations, and it reached a maximum value when the ratio of zein/wheat gluten was 20%, but had a minimum value when the ratio of liquid to solid was 8:1; Water Vapor Permeability (WVP) increased with an increase of glycerol concentration and the ratio of liquid to solid and ethanol concentration, but it decreased with increasing zein/wheat gluten ratio, heat treatment temperature, and pH of the film forming solution. Full article

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292 KiB

Open AccessArticle

Protective Effect of Ischemic Postconditioning against Ischemia Reperfusion-Induced Myocardium Oxidative Injury in IR Rats

by Li Zhang, Jiangwei Ma and Huajin Liu

Molecules 2012, 17(4), 3805-3817; https://doi.org/10.3390/molecules17043805 - 27 Mar 2012

Cited by 25 | Viewed by 6928

Abstract

Brief episodes of myocardial ischemia-reperfusion (IR) employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion [...] Read more.

Brief episodes of myocardial ischemia-reperfusion (IR) employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR)-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA) level, and increased myocardium Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats. Full article

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310 KiB

Open AccessArticle

1D ¹³C-NMR Data as Molecular Descriptors in Spectra — Structure Relationship Analysis of Oligosaccharides

by Florbela Pereira

Molecules 2012, 17(4), 3818-3833; https://doi.org/10.3390/molecules17043818 - 28 Mar 2012

Cited by 3 | Viewed by 7665

Abstract

Spectra-structure relationships were investigated for estimating the anomeric configuration, residues and type of linkages of linear and branched trisaccharides using ¹³C-NMR chemical shifts. For this study, 119 pyranosyl trisaccharides were used that are trimers of the α or β anomers of D-glucose, [...] Read more.

Spectra-structure relationships were investigated for estimating the anomeric configuration, residues and type of linkages of linear and branched trisaccharides using ¹³C-NMR chemical shifts. For this study, 119 pyranosyl trisaccharides were used that are trimers of the α or β anomers of D-glucose, D-galactose, D-mannose, L-fucose or L-rhamnose residues bonded through a or b glycosidic linkages of types 1→2, 1→3, 1→4, or 1→6, as well as methoxylated and/or N-acetylated amino trisaccharides. Machine learning experiments were performed for: (1) classification of the anomeric configuration of the first unit, second unit and reducing end; (2) classification of the type of first and second linkages; (3) classification of the three residues: reducing end, middle and first residue; and (4) classification of the chain type. Our previously model for predicting the structure of disaccharides was incorporated in this new model with an improvement of the predictive power. The best results were achieved using Random Forests with 204 di- and trisaccharides for the training set—it could correctly classify 83%, 90%, 88%, 85%, 85%, 75%, 79%, 68% and 94% of the test set (69 compounds) for the nine tasks, respectively, on the basis of unassigned chemical shifts. Full article

(This article belongs to the Special Issue Advances in Carbohydrate Chemistry 2012)

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Open AccessArticle

Aminodi(hetero)arylamines in the Thieno[3,2-b]pyridine Series: Synthesis, Effects in Human Tumor Cells Growth, Cell Cycle Analysis, Apoptosis and Evaluation of Toxicity Using Non-Tumor Cells

by Ricardo C. Calhelha, Isabel C. F. R. Ferreira, Daniela Peixoto, Rui M. V. Abreu, Luís A. Vale-Silva, Eugénia Pinto, Raquel T. Lima, M. Inês Alvelos, M. Helena Vasconcelos and Maria-João R. P. Queiroz

Molecules 2012, 17(4), 3834-3843; https://doi.org/10.3390/molecules17043834 - 28 Mar 2012

Cited by 17 | Viewed by 8018

Abstract

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth [...] Read more.

Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG₂ (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH₂ group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI₅₀ values (1.30–1.63 µM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels. Full article

(This article belongs to the Collection Bioactive Compounds)

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Open AccessArticle

Baicalin Induces Apoptosis in SW620 Human Colorectal Carcinoma Cells in Vitro and Suppresses Tumor Growth in Vivo

by Wen-Cheng Chen, Tsu-Hsiang Kuo, Yi-Shiuan Tzeng and Ying-Chieh Tsai

Molecules 2012, 17(4), 3844-3857; https://doi.org/10.3390/molecules17043844 - 29 Mar 2012

Cited by 59 | Viewed by 9001

Abstract

In the United States, colorectal cancer (CRC) is the second most frequent malignancy and the fourth most common cause of cancer death. Baicalin, a flavone derivative isolated and purified from the dry root of Scutellaria, was assessed for its antitumor effects in [...] Read more.

In the United States, colorectal cancer (CRC) is the second most frequent malignancy and the fourth most common cause of cancer death. Baicalin, a flavone derivative isolated and purified from the dry root of Scutellaria, was assessed for its antitumor effects in human SW620 CRC cells. Baicalin (200 μM) inhibited proliferation of SW620 cells. Baicalin (200 μM) increased activities of caspase-3, -8, and -9 in SW620 cells. Furthermore, flow cytometric analysis of baicalin-treated SW620 cells showed an increase in sub-G1 cells, and the dihydroethidium assay showed significant enhancement of intracellular peroxide production in baicalin-treated cells. Addition of N-acetylcysteine prevented most of the baicalin-induced apoptosis, which in turn mediated cytotoxicity in human SW620 cells. In vivo, baicalin (50 mg/kg/day, i.p.) treatment inhibited 55% of tumor growth in xenografted nude mice by 4 weeks, compared to that of the vehicle control (p < 0.05). Baicalin had no noteworthy influence on body weight. Thus, we suggest the development of baicalin as a potential leading antitumor agent in CRC. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Characterization of Fullerene Nanowhiskers by Liquid-Liquid Interfacial Precipitation: Influence of C₆₀ Solubility

by Marappan Sathish and Kun’ichi Miyazawa

Molecules 2012, 17(4), 3858-3865; https://doi.org/10.3390/molecules17043858 - 29 Mar 2012

Cited by 42 | Viewed by 9494

Abstract

Fullerene nanowhiskers (FNWs) composed of C₆₀ fullerene molecules were prepared using the liquid–liquid interfacial precipitation (LLIP) method in the carbon-disulfide (CS₂) and isopropyl alcohol (IPA) system. The electron microscopic images reveal the formation of non-tubular FNWs. The X-ray diffraction (XRD) [...] Read more.

Fullerene nanowhiskers (FNWs) composed of C₆₀ fullerene molecules were prepared using the liquid–liquid interfacial precipitation (LLIP) method in the carbon-disulfide (CS₂) and isopropyl alcohol (IPA) system. The electron microscopic images reveal the formation of non-tubular FNWs. The X-ray diffraction (XRD) pattern studies indicate the presence of fcc crystalline structure and unusual triclinic structure in the FNWs. The selected area electron diffraction pattern (SAED) analysis demonstrates the existence of triclinic and electron beam assisted fcc to tetragonal crystalline phase transformation. The formation of triclinic structure might be validated due to the partial polymerization of FNWs at C₆₀ saturated CS₂-IPA interface. The high solubility of C₆₀ in CS₂ solvent system results in partial polymerization of FNWs. The polymerization of fullerene molecules in the FNWs has been further confirmed using Raman spectroscopy. Full article

(This article belongs to the Special Issue Fullerene Chemistry)

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Open AccessArticle

Essential Oil from Cryptomeria japonica Induces Apoptosis in Human Oral Epidermoid Carcinoma Cells via Mitochondrial Stress and Activation of Caspases

by Jeong-Dan Cha and Ji-Young Kim

Molecules 2012, 17(4), 3890-3901; https://doi.org/10.3390/molecules17043890 - 30 Mar 2012

Cited by 24 | Viewed by 7265

Abstract

Cryptomeria japonica D. Don (C. japonica) has been used in traditional medicines from Asia for a variety of indications, including liver ailments, and an antitussive, and for its antiulcer activities. We examined the cell viability and apoptosis of KB cells treated [...] Read more.

Cryptomeria japonica D. Don (C. japonica) has been used in traditional medicines from Asia for a variety of indications, including liver ailments, and an antitussive, and for its antiulcer activities. We examined the cell viability and apoptosis of KB cells treated with C. japonica essential oil at several concentrations for 12 h by MTT assay, Hoechst-33258 dye staining, DNA fragmentation, flow cytometry (cell cycle), and Western blotting for mitochondria stress, activation of caspases, and poly (ADP-ribose) polymerase. The essential oil induced the apoptosis of KB cells in a dose-dependent manner, which was verified by DNA fragmentation, appearance of apoptotic bodies, and the sub-G1 ratio. The essential oil also induced rapid and transient caspase-3 activity and cleavage of PARP of the KB cells. Treating the cells with the oil also caused changes in the mitochondrial level of the Bcl-2 family proteins such as Bcl-2 and Bax, thereby inducing the release of cytochrome c into the cytosol. The essential oil of C. japonica may have potential as a cancer chemopreventive and therapeutic agent. Full article

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Open AccessArticle

Inhibition of Melanogenesis Versus Antioxidant Properties of Essential Oil Extracted from Leaves of Vitex negundo Linn and Chemical Composition Analysis by GC-MS

by Huey-Chun Huang, Tzu-Yun Chang, Long-Zen Chang, Hsiao-Fen Wang, Kuang-Hway Yih, Wan-Yu Hsieh and Tsong-Min Chang

Molecules 2012, 17(4), 3902-3916; https://doi.org/10.3390/molecules17043902 - 30 Mar 2012

Cited by 57 | Viewed by 10361

Abstract

This study was aimed at investigating the antimelanogenic and antioxidative properties of the essential oil extracted from leaves of V. negundo Linn and the analysis of the chemical composition of this essential oil. The efficacy of the essential oil was evaluated spectrophotometrically, whereas [...] Read more.

This study was aimed at investigating the antimelanogenic and antioxidative properties of the essential oil extracted from leaves of V. negundo Linn and the analysis of the chemical composition of this essential oil. The efficacy of the essential oil was evaluated spectrophotometrically, whereas the volatile chemical compounds in the essential oil were analyzed by gas chromatography-mass spectrometry (GC-MS). The results revealed that the essential oil effectively suppresses murine B16F10 tyrosinase activity and decreases the amount of melanin in a dose-dependent manner. Additionally, the essential oil significantly scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals, and showed potent reducing power versus metal-ion chelating properties in a dose-dependent pattern. The chemical constituents in the essential oil are sesquiterpenes (44.41%), monoterpenes (19.25%), esters (14.77%), alcohols (8.53%), aromatic compound (5.90%), ketone (4.96%), ethers (0.4%) that together account for 98.22% of its chemical composition. It is predicted that the aromatic compound in the essential oil may contribute to its antioxidant activities. The results indicated that essential oil extracted from V. negundo Linn leaves decreased melanin production in B16F10 melanoma cells and showed potent antioxidant activities. The essential oil can thereby serve as an inhibitor of melanin synthesis and could also act as a natural antioxidant. Full article

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Open AccessArticle

Antioxidant, Antimicrobial Properties and Phenolics of Different Solvent Extracts from Bark, Leaves and Seeds of Pongamia pinnata (L.) Pierre

by Zahid Iqbal Sajid, Farooq Anwar, Ghulam Shabir, Ghulam Rasul, Khalid M. Alkharfy and Anwarul-Hassan Gilani

Molecules 2012, 17(4), 3917-3932; https://doi.org/10.3390/molecules17043917 - 30 Mar 2012

Cited by 58 | Viewed by 11766

Abstract

This study appraises the antioxidant and antimicrobial attributes of various solvent extracts (absolute methanol, aqueous methanol, absolute ethanol, aqueous ethanol, absolute acetone, aqueous acetone, and deionized water) from bark, leaves and seeds of Pongamia pinnata (L.) Pierre. Maximum extraction yield of antioxidant components [...] Read more.

This study appraises the antioxidant and antimicrobial attributes of various solvent extracts (absolute methanol, aqueous methanol, absolute ethanol, aqueous ethanol, absolute acetone, aqueous acetone, and deionized water) from bark, leaves and seeds of Pongamia pinnata (L.) Pierre. Maximum extraction yield of antioxidant components from bark (16.31%), leaves (11.42%) and seeds (21.51%) of P. pinnata was obtained using aqueous methanol (20:80). Of the extracts tested, the bark extract, obtained with aqueous methanol, exhibited greater levels of total phenolics [6.94 g GAE/100 g dry weight (DW)], total flavonoids (3.44 g CE/100 g DW), inhibition of linoleic acid peroxidation (69.23%) and DPPH radical scavenging activity (IC₅₀ value, 3.21 μg/mL), followed by leaves and seeds extracts. Bark extract tested against a set of bacterial and fungal strains also revealed the strongest antimicrobial activity with the largest inhibition zone and lowest minimum inhibitory concentration (MIC). HPLC analysis of aqueous methanol extracts from bark, leaves and seeds indicated the presence of protocatechuic, ellagic, ferulic, gallic, gentisic, 4-hydroxybenzoic and 4-hydroxycinnamic acids in bark (1.50–6.70 mg/100 g DW); sorbic, ferulic, gallic, salicylic and p-coumaric acids in leaves (1.18–4.71 mg/100 g DW); vanillic, gallic and tannic acids in seeds (0.52–0.65 mg/100 g DW) as the main phenolic acids. The present investigation concludes that the tested parts of P. pinnata, in particular the bark, have strong potential for the isolation of antioxidant and antimicrobial agents for functional food and pharmaceutical uses. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Biological Evaluation of Novel Benzothiazole-2-thiol Derivatives as Potential Anticancer Agents

by Xuan-Hong Shi, Zhao Wang, Yong Xia, Ting-Hong Ye, Mei Deng, You-Zhi Xu, Yu-Quan Wei and Luo-Ting Yu

Molecules 2012, 17(4), 3933-3944; https://doi.org/10.3390/molecules17043933 - 30 Mar 2012

Cited by 55 | Viewed by 8656

Abstract

A series of novel benzothiazole-2-thiol derivatives were synthesized and their structures determined by ¹H-NMR, ¹³C-NMR and HRMS (ESI). The effects of all compounds on a panel of different types of human cancer cell lines were investigated. Among them, pyridinyl-2-amine linked benzothiazole-2-thiol [...] Read more.

A series of novel benzothiazole-2-thiol derivatives were synthesized and their structures determined by ¹H-NMR, ¹³C-NMR and HRMS (ESI). The effects of all compounds on a panel of different types of human cancer cell lines were investigated. Among them, pyridinyl-2-amine linked benzothiazole-2-thiol compounds 7d, 7e, 7f and 7i exhibited potent and broad-spectrum inhibitory activities. Compound 7e displayed the most potent anticancer activity on SKRB-3 (IC₅₀ = 1.2 nM), SW620 (IC₅₀ = 4.3 nM), A549 (IC₅₀ = 44 nM) and HepG2 (IC₅₀ = 48 nM) and was found to induce apoptosis in HepG2 cancer cells. Full article

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Open AccessArticle

Enzymatic Activity Enhancement of Non-Covalent Modified Superoxide Dismutase and Molecular Docking Analysis

by Yan-Zi Qiu, Zong-Hua Huang and Fa-Jun Song

Molecules 2012, 17(4), 3945-3956; https://doi.org/10.3390/molecules17043945 - 30 Mar 2012

Cited by 14 | Viewed by 7227

Abstract

The enzyme activity of superoxide dismutase was improved in the pyrogallol autoxidation system by about 27%, after interaction between hydroxypropyl-β-cyclo- dextrin and superoxide dismutase. Fluorescence spectrometry was used to study the interaction between hydroxypropyl-β-cyclodextrin and superoxide dismutase at different temperatures. By doing this, [...] Read more.

The enzyme activity of superoxide dismutase was improved in the pyrogallol autoxidation system by about 27%, after interaction between hydroxypropyl-β-cyclo- dextrin and superoxide dismutase. Fluorescence spectrometry was used to study the interaction between hydroxypropyl-β-cyclodextrin and superoxide dismutase at different temperatures. By doing this, it can be found that these interactions increase fluorescence sensitivity. In the meantime, the synchronous fluorescence intensity revealed the interaction sites to be close to the tryptophan (Trp) and tyrosine (Tyr) residues of superoxide dismutase. Furthermore, molecular docking was applied to explore the binding mode between the ligands and the receptor. This suggested that HP-β-CD interacted with the B ring, G ring and the O ring and revealed that the lysine (Lys) residues enter the nanocavity. It was concluded that the HP-β-CD caused specific conformational changes in SOD by non-covalent modification. Full article

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Open AccessCommunication

4-N,N-Dimethylaminopyridine Promoted Selective Oxidation of Methyl Aromatics with Molecular Oxygen

by Zhan Zhang, Jin Gao, Feng Wang and Jie Xu

Molecules 2012, 17(4), 3957-3968; https://doi.org/10.3390/molecules17043957 - 30 Mar 2012

Cited by 8 | Viewed by 11131

Abstract

4-N,N-Dimethylaminopyridine (DMAP) as catalyst in combination with benzyl bromide was developed for the selective oxidation of methyl aromatics. DMAP exhibited higher catalytic activity than other pyridine analogues, such as 4-carboxypyridine, 4-cyanopyridine and pyridine. The sp³ hybrid carbon-hydrogen (C–H) [...] Read more.

4-N,N-Dimethylaminopyridine (DMAP) as catalyst in combination with benzyl bromide was developed for the selective oxidation of methyl aromatics. DMAP exhibited higher catalytic activity than other pyridine analogues, such as 4-carboxypyridine, 4-cyanopyridine and pyridine. The sp³ hybrid carbon-hydrogen (C–H) bonds of different methyl aromatics were successfully oxygenated with molecular oxygen. The real catalyst is due to the formation of a pyridine onium salt from the bromide and DMAP. The onium salt was well characterized by NMR and the reaction mechanism was discussed. Full article

(This article belongs to the Special Issue Organocatalysis)

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Open AccessArticle

Synthesis and Herbicidal Activity Evaluation of Novel β-Carboline Derivatives

by Qunfang Weng, Jingfei Huang, Yong Zeng, Yueye Deng and Meiying Hu

Molecules 2012, 17(4), 3969-3980; https://doi.org/10.3390/molecules17043969 - 2 Apr 2012

Cited by 10 | Viewed by 7244

Abstract

Based on the original structure of harmine, several novel 1,2,3,4-tetrahydro-β-carboline, β-carboline and 1-substituted-β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were designed and synthesized to investigate the structure-activity relationship of their analogues. All of the compounds were characterized by infrared (IR), proton [...] Read more.

Based on the original structure of harmine, several novel 1,2,3,4-tetrahydro-β-carboline, β-carboline and 1-substituted-β-carboline derivatives bearing a substituted carbohydrazide group at C-3 were designed and synthesized to investigate the structure-activity relationship of their analogues. All of the compounds were characterized by infrared (IR), proton and carbon nuclear magnetic resonance (¹H-NMR, ¹³C-NMR), and mass spectroscopy (MS). The bioassay tests showed that N'-benzylidene-1-phenyl-β-carboline-3-carbohydrazide (C₂₅H₁₈N₄O, m.w. 390.4) (c2) and N'-(4-trifluoromethyl-benzylidene)-1-phenyl-β-carboline-3-carbohydrazide (C₂₆H₁₇N₄OF₃, m.w. 458) (d2) exhibited good inhibitory activity against dicotyledonous and monocotyledonous weeds, with EC₅₀ values of 4.83 µM and 14.25 µM, respectively. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Diverse Effects of β-Carotene on Secretion and Expression of VEGF in Human Hepatocarcinoma and Prostate Tumor Cells

by Huei-Yan Chen, Shu-Ming Huang, Chih-Min Yang and Miao-Lin Hu

Molecules 2012, 17(4), 3981-3988; https://doi.org/10.3390/molecules17043981 - 2 Apr 2012

Cited by 15 | Viewed by 8004

Abstract

Oral administration of β-carotene (BC) was found to exert opposite effects on plasma levels of vascular endothelial growth factor (VEGF) in two animal models. One study in nude mice injected via tail vein with hepatocarcinoma SK-Hep-1 cells showed that BC decreases the plasma [...] Read more.

Oral administration of β-carotene (BC) was found to exert opposite effects on plasma levels of vascular endothelial growth factor (VEGF) in two animal models. One study in nude mice injected via tail vein with hepatocarcinoma SK-Hep-1 cells showed that BC decreases the plasma VEGF level, whereas the other study in nude mice injected subcutaneously with prostate tumor PC-3 cells showed that BC increases the plasma VEGF level. Herein we investigated whether BC (0.5–20 μM) possesses diverse effects on VEGF secretion in SK-Hep-1, PC-3 and melanoma B16F10 cells. We found that incubation of SK-Hep-1 cells with BC (1–20 μM) for 6 h significantly decreased VEGF secretion, whereas BC (1–10 μM) significantly increased the VEGF secretion in PC-3 cells. However, these effects disappeared at 12 h of incubation. Similar effects occurred in VEGF mRNA and protein expression after treatment of SK-Hep-1 and PC-3 cells with BC for 6 h. In contrast, BC (0.5–20 μM) did not affect mRNA and protein expression and secretion of VEGF in B16F10 cells. We also found that the proliferation of SK-Hep-1 and B16F10 cells was significantly inhibited by 20 μM BC at 6 and 12 h of incubation, whereas the proliferation of PC-3 cells was significantly inhibited by 20 μM BC at 12 h of incubation. In summary, the present study demonstrated the tumor-specific effect of BC on VEGF secretion in different cancer cell lines. Full article

(This article belongs to the Special Issue Carotenoids)

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Open AccessArticle

A Simple Halide-to-Anion Exchange Method for Heteroaromatic Salts and Ionic Liquids

by Ermitas Alcalde, Immaculada Dinarès, Anna Ibáñez and Neus Mesquida

Molecules 2012, 17(4), 4007-4027; https://doi.org/10.3390/molecules17044007 - 2 Apr 2012

Cited by 60 | Viewed by 17543

Abstract

A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A⁻ form) in non-aqueous media. The anion loading of the AER (OH⁻ form) was [...] Read more.

A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A⁻ form) in non-aqueous media. The anion loading of the AER (OH⁻ form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A⁻ form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity of the targeted ion pair for the counteranion swap, organic solvents with variable polarity were used, such as CH₃OH, CH₃CN and the dipolar nonhydroxylic solvent mixture CH₃CN:CH₂Cl₂ (3:7) and the anion exchange was equally successful with both lipophilic cations and anions. Full article

(This article belongs to the Collection Ionic Liquids)

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Open AccessArticle

Naucline, a New Indole Alkaloid from the Bark of Nauclea officinalis

by Sook Yee Liew, Mat Ropi Mukhtar, A. Hamid A. Hadi, Khalijah Awang, Mohd Rais Mustafa, Kazumasa Zaima, Hiroshi Morita and Marc Litaudon

Molecules 2012, 17(4), 4028-4036; https://doi.org/10.3390/molecules17044028 - 2 Apr 2012

Cited by 30 | Viewed by 9608

Abstract

A new indole alkaloid, naucline (1) together with four known alkaloids, angustine (2), angustidine (3), nauclefine (4) and naucletine (5), were isolated from the bark of Nauclea officinalis. The structures of all [...] Read more.

A new indole alkaloid, naucline (1) together with four known alkaloids, angustine (2), angustidine (3), nauclefine (4) and naucletine (5), were isolated from the bark of Nauclea officinalis. The structures of all isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS-IT-TOF. In addition to that of alkaloid 1, the complete ¹³C-NMR data of naucletine (5) were also reported. Naucline (1) showed a moderate vasorelaxant activity (90% relaxation at 1 × 10⁻⁵ M) whereas, angustine (2), nauclefine (4), and naucletine (5) showed potent vasorelaxant activity (more than 90% relaxation at 1 × 10⁻⁵ M) on an isolated rat aorta. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Phytotoxic Effects and a Phytotoxin from the Invasive Plant Xanthium italicum Moretti

by Hua Shao, Xiaoli Huang, Xiaoyi Wei and Chi Zhang

Molecules 2012, 17(4), 4037-4046; https://doi.org/10.3390/molecules17044037 - 2 Apr 2012

Cited by 26 | Viewed by 10617

Abstract

The allelopathic effects of different parts of the plant Xanthium italicum Moretti were evaluated by conducting bioassays against two dicot plants, amaranth (Amaranthus mangostanus L.) and lettuce (Lectuca sativa L.), and two monocot plants, wheat (Triticum aestivum Linn) and [...] Read more.

The allelopathic effects of different parts of the plant Xanthium italicum Moretti were evaluated by conducting bioassays against two dicot plants, amaranth (Amaranthus mangostanus L.) and lettuce (Lectuca sativa L.), and two monocot plants, wheat (Triticum aestivum Linn) and ryegrass (Lolium multiforum). Leaf and fruit extract possessed the strongest biological activity, killing all seeds of four test species at 0.05 g/mL concentration. Fruits were chosen for further investigation because of their high biomass. This led to the isolation and identification of a phytotoxin—Xanthinosin—a known sesquiterpene lactone. Xanthinosin significantly affected seedling growth of all test species at 160 µM concentration. Cultivating seeds in 800 μM xanthinosin solution resulted in a great decrease in seedling growth of all test species, especially for the two dicot plants, amaranth and lettuce, whose root length was inhibited by 78% and 89%, respectively. By comparison, the numbers were 69% lower for wheat, and 66% for ryegrass, two monocot plants. When treated with 4 mM xanthinosin solution, seed germination of all test plants was almost completely inhibited. The possibility of utilizing xanthinosin as an eco-friendly herbicide was discussed. Full article

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Open AccessArticle

Pressurized Liquid Extraction of Coumarins from Fruits of Heracleum leskowii with Application of Solvents with Different Polarity under Increasing Temperature

by Krystyna Skalicka-Woźniak and Kazimierz Głowniak

Molecules 2012, 17(4), 4133-4141; https://doi.org/10.3390/molecules17044133 - 5 Apr 2012

Cited by 32 | Viewed by 8469

Abstract

Coumarins are nowadays an important group of organic compounds from natural sources that are useful in a number of fields. Because they possess different pharmacological properties, finding the proper extraction conditions for their separation from plant matrices is a very important step. In [...] Read more.

Coumarins are nowadays an important group of organic compounds from natural sources that are useful in a number of fields. Because they possess different pharmacological properties, finding the proper extraction conditions for their separation from plant matrices is a very important step. In this report Pressurized Liquid Extraction (PLE) under different temperature conditions and with different types of extraction solvents were tested. As a matrix, fruits of Heracleum leskowii have been used. A simple reverse phase high-performance liquid chromatographic method (RP-HPLC) coupled with a photodiode array detector (DAD) has been developed for separation and quantitative analysis of the main coumarins. Umbelliferone, xanthotoxin, angelicin, isopimpinellin, bergapten, imperatorin and isoimperatorin were investigated. Bergapten and imperatorin were dominant in almost all extracts in the range of 9.92 ± 0.02–20.93 ± 0.06 and 12.19 ± 0.98–19.07 ± 0.03 mg/100 g, respectively. Dichloromethane and methanol were chosen as the most proper suitable solvents for extraction of coumarins. By increasing the temperature the amount of extracted coumarins increases in petroleum ether and dichloromethane extracts. Full article

(This article belongs to the Special Issue Coumarins and Xanthones)

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Open AccessArticle

Antioxidant, Antitubercular and Cytotoxic Activities of Piper imperiale

by Luis E. Diaz, Diego R. Munoz, Rosa E. Prieto, Sergio A. Cuervo, Diego L. Gonzalez, Juan D. Guzman and Sanjib Bhakta

Molecules 2012, 17(4), 4142-4157; https://doi.org/10.3390/molecules17044142 - 5 Apr 2012

Cited by 23 | Viewed by 10049

Abstract

Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower [...] Read more.

Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to 6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin, ferulic acid, resveratrol and quercetin were identified and quantified by HPLC. DPPH and ABTS assays showed high antioxidant activity of the leaf extract (EC_50ABTS = 15.6 µg/mL, EC_50DPPH = 27.3 µg/mL) with EC₅₀ in the same order of magnitude as the hydroxyquinone (EC_50ABTS = 10.2 µg/mL, EC_50DPPH = 15.7 µg/mL). The flower extract showed strong antimicrobial activity against Mycobacterium tuberculosis H₃₇Rv. All the extracts exhibited dose-dependent cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper extract has been found to be highly active against M. tuberculosis. This study shows the biological potential of Piper imperiale extracts and gives way to bio-guided studies with well-defined biological activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthetic Study on the Relationship Between Structure and Sweet Taste Properties of Steviol Glycosides

by Mani Upreti, Grant Dubois and Indra Prakash

Molecules 2012, 17(4), 4186-4196; https://doi.org/10.3390/molecules17044186 - 5 Apr 2012

Cited by 28 | Viewed by 9998

Abstract

The structure activity relationship between the C₁₆-C₁₇ methylene double bond on the aglycone of steviol glycosides and the corresponding impact on their sweet taste has been reported here for the first time. It has been observed that converting stevioside and [...] Read more.

The structure activity relationship between the C₁₆-C₁₇ methylene double bond on the aglycone of steviol glycosides and the corresponding impact on their sweet taste has been reported here for the first time. It has been observed that converting stevioside and rebaudioside A to their corresponding ketones by switching the doubly bonded methylene on C-17 for a ketone group actually removes the sweet taste properties of these molecules completely. Regenerating the original molecules tends to restore the sweet taste of both the steviol glycosides. Thus this C₁₆-C₁₇ methylene double bond in rebaudioside A and stevioside can be regarded as a pharmacophore essential for the sweetness property of these molecules. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

(−)-Kunstleramide, a New Antioxidant and Cytotoxic Dienamide from the Bark of Beilschmiedia kunstleri Gamble

by Abbas Mollataghi, A. Hamid A. Hadi and Shiau-Chuen Cheah

Molecules 2012, 17(4), 4197-4208; https://doi.org/10.3390/molecules17044197 - 5 Apr 2012

Cited by 19 | Viewed by 8039

Abstract

A new dienamide, (2E,4E)-7-(3',4'-dimethoxyphenyl)-N-ethyl-6-(R)-hydroxyhepta- 2,4-dienamide, named (-)-kunstleramide (1), were isolated from the bark of Beilschmiedia kunstleri Gamble together with one neolignan: (+)-kunstlerone (2) and seven known alkaloids: (+)-nornuciferine (3), [...] Read more.

A new dienamide, (2E,4E)-7-(3',4'-dimethoxyphenyl)-N-ethyl-6-(R)-hydroxyhepta- 2,4-dienamide, named (-)-kunstleramide (1), were isolated from the bark of Beilschmiedia kunstleri Gamble together with one neolignan: (+)-kunstlerone (2) and seven known alkaloids: (+)-nornuciferine (3), (-)-isocaryachine (4), (+)-cassythicine (5), (+)-laurotetanine (6), (+)-boldine (7), noratherosperminine (8), (+)-N-demethylphyllocaryptine (9). Their structures were established from spectroscopic techniques, most notably 1D- and 2D-NMR, UV, IR, OR, circular dichroism (CD) spectra and LCMS-IT-TOF. (-)-Kunstleramide (1) exhibited very poor dose-dependent inhibition of DPPH activity, with an IC₅₀ value of 179.5 ± 4.4 μg/mL, but showed a moderate cytotoxic effect on MTT assays of A375, A549, HT-29, PC-3 and WRL-68 with EC₅₀ values of 64.65, 44.74, 55.94, 73.87 and 70.95 µg/mL, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and NMR Spectral Studies of the 7-C₆₀-Adduct of N,N-(Tetrachlorophthaloyl) Dehydroabietylamine

by Zhi Zhou and Zhongxiang Lin

Molecules 2012, 17(4), 4209-4218; https://doi.org/10.3390/molecules17044209 - 5 Apr 2012

Cited by 3 | Viewed by 7429

Abstract

The 7-C₆₀-adduct of N,N-(tetrachlorophthaloyl)dehydroabietylamine was synthesized for the first time and characterized by IR, UV-vis, mass and NMR spectral studies. The ¹H-NMR and ¹³C-NMR resonance signals of the new compound are unambiguously assigned by using homo- [...] Read more.

The 7-C₆₀-adduct of N,N-(tetrachlorophthaloyl)dehydroabietylamine was synthesized for the first time and characterized by IR, UV-vis, mass and NMR spectral studies. The ¹H-NMR and ¹³C-NMR resonance signals of the new compound are unambiguously assigned by using homo- and heteronuclear 2D NMR spectroscopic techniques such as COSY, ROESY, HSQC and HMBC. The C₁ symmetric structure with 6,6-junction of compound was determined. Full article

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Open AccessArticle

A Novel Antioxidant Isobenzofuranone Derivative from Fungus Cephalosporium sp.AL031

by Xiang-Zhong Huang, Yun Zhu, Xiao-Li Guan, Kai Tian, Jun-Ming Guo, Hong-Bin Wang and Guang-Miao Fu

Molecules 2012, 17(4), 4219-4224; https://doi.org/10.3390/molecules17044219 - 5 Apr 2012

Cited by 33 | Viewed by 7241

Abstract

Bioassay-guided fractionation of metabolites from the fungus Cephalosporium sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1), together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4 [...] Read more.

Bioassay-guided fractionation of metabolites from the fungus Cephalosporium sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1), together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4). The structure of the new compound 1 was determined based on MS, 1D and 2D NMR spectral data. Compounds 1–4 showed potent antioxidant activity with EC₅₀ values of 10, 7, 22 and 5 μM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Enantioseparation and Absolute Configuration Determination of Angular-Type Pyranocoumarins from Peucedani Radix Using Enzymatic Hydrolysis and Chiral HPLC-MS/MS Analysis

by Yue-Lin Song, Qing-Wen Zhang, Ya-Ping Li, Ru Yan and Yi-Tao Wang

Molecules 2012, 17(4), 4236-4251; https://doi.org/10.3390/molecules17044236 - 10 Apr 2012

Cited by 44 | Viewed by 8503

Abstract

Angular-type pyranocoumarins from Peucedani Radix (Chinese name: Qian-hu) have exhibited potential for use on treatment of cancer and pulmonary hypertension. Due to the existence of C-3′ and C-4′ chiral centers, compounds belonging to this chemical type commonly exist in enantiomers and/or diastereoisomers, which [...] Read more.

Angular-type pyranocoumarins from Peucedani Radix (Chinese name: Qian-hu) have exhibited potential for use on treatment of cancer and pulmonary hypertension. Due to the existence of C-3′ and C-4′ chiral centers, compounds belonging to this chemical type commonly exist in enantiomers and/or diastereoisomers, which may elicit distinct activities during their interactions with the human body. In the present study, a new method, which combines enzymatic hydrolysis with chiral LC-MS/MS analysis, has been developed to determine the absolute configurations of these angular-type pyranocoumarins. Pyranocoumarins isolated from Qian-hu, their enantiomers, or metabolites were individually incubated with rat liver microsomes. As the common end product from enzymatic hydrolysis of all tested pyranocoumarins, cis-khellactone was collected and its absolute configuration was determined by comparison with (+)-cis-khellactone and (−)-cis-khellactone using chiral LC-MS/MS. The absolute configurations of all tested parent pyranocoumarins were determined by combination of LC-MS/MS, NMR and polarimetric analysis. The results revealed that the metabolite cis-khellactone retained the same absolute configurations of the stereogenic carbons as the respective parent compound. This method was proven to be rapid and sensitive and also has advantages in discriminating single enantiomers and mixtures of optical isomers with different ratios. Full article

(This article belongs to the Special Issue Coumarins and Xanthones)

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Open AccessArticle

(E)-5-Styryl-1H-indole and (E)-6-Styrylquinoline Derivatives Serve as Probes for β-Amyloid Plaques

by Yang Yang, Hong-Mei Jia and Bo-Li Liu

Molecules 2012, 17(4), 4252-4265; https://doi.org/10.3390/molecules17044252 - 10 Apr 2012

Cited by 21 | Viewed by 8082

Abstract

We report the synthesis and biological evaluation of novel (E)-5-styryl-1H-indole and (E)-6-styrylquinoline derivatives as probes for imaging β-amyloid (Aβ) plaques. These derivatives showed binding affinities for Aβ_1–40 aggregates with K_i values varying from 4.1 to [...] Read more.

We report the synthesis and biological evaluation of novel (E)-5-styryl-1H-indole and (E)-6-styrylquinoline derivatives as probes for imaging β-amyloid (Aβ) plaques. These derivatives showed binding affinities for Aβ_1–40 aggregates with K_i values varying from 4.1 to 288.4 nM. (E)-5-(4-iodostyryl)-1H-indole (8) clearly stained Aβ plaques in the brain sections of Alzheimer’s disease (AD) model mice (APP/PS1). Furthermore, autoradiography for [¹²⁵I]8 displayed intense and specific labeling of Aβ plaques in the brain sections mentioned above with low background. In biodistribution experiments using normal mice [¹²⁵I]8 showed high initial brain uptake followed by rapid washout (4.27 and 0.64% ID/g at 2 and 30 min post injection, respectively). These findings suggests that [¹²³I]8 may be a potential SPECT imaging agent for detecting Aβ plaques in AD brain. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

One-Pot Synthesis of Disperse Dyes Under Microwave Irradiation: Dyebath Reuse in Dyeing of Polyester Fabrics

by Alya M. Al-Etaibi, Morsy A. El-Apasery, Huda M. Mahmoud and Nouria A. Al-Awadi

Molecules 2012, 17(4), 4266-4280; https://doi.org/10.3390/molecules17044266 - 10 Apr 2012

Cited by 24 | Viewed by 7435

Abstract

A series of 4-hydroxyphenylazopyrazolopyrimidine disperse dyes were prepared via one-pot reactions of p-hydroxyphenylhydrazone, hydrazine hydrate, and acetylacetone or enaminones using microwave irradiation as an energy source. Structural assignments of the dyes were confirmed by X-ray crystallographic structure determination. Instead of discharging the [...] Read more.

A series of 4-hydroxyphenylazopyrazolopyrimidine disperse dyes were prepared via one-pot reactions of p-hydroxyphenylhydrazone, hydrazine hydrate, and acetylacetone or enaminones using microwave irradiation as an energy source. Structural assignments of the dyes were confirmed by X-ray crystallographic structure determination. Instead of discharging the dyebath after each dyeing cycle, the residual dyebath was spectrophotometrically analyzed and then pH readjusted for a repeat dyeing with longer time. Fastness of the dyed samples was measured after each recycle. Most of the dyed fabrics tested displayed good light fastness and excellent fastness to washing and perspiration. Finally, the biological activity of the synthesized dyes against Gram positive bacteria, Gram negative bacteria and yeast were evaluated. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Evaluation of Antioxidant and Immunity Activities of Quercetin in Isoproterenol-Treated Rats

by Hui Liu, Lei Zhang and Shaoping Lu

Molecules 2012, 17(4), 4281-4291; https://doi.org/10.3390/molecules17044281 - 10 Apr 2012

Cited by 57 | Viewed by 7419

Abstract

The present study was designed to evaluate the effect of quercetin on myocardial oxidative stress and immunity function impairment induced by isoproterenol in rats. To induce myocardial ischemia, Wistar rats were subcutaneously injected with isoproterenol (70 mg/kg). Blood immunity index, cardiac marker enzymes [...] Read more.

The present study was designed to evaluate the effect of quercetin on myocardial oxidative stress and immunity function impairment induced by isoproterenol in rats. To induce myocardial ischemia, Wistar rats were subcutaneously injected with isoproterenol (70 mg/kg). Blood immunity index, cardiac marker enzymes and antioxidative parameters in hearts were measured. It was found that the levels of blood AST, creatine kinase, NO, NOS, IL-10, IL-1, IL-8 and lactate dehydrogenase in isoproterenol-treated rats were significantly increased. The rats administrated with isoproterenol showed the declines in myocardial antioxidant enzymes activities. Administration of quercetin significantly ameliorated myocardial oxidative injury and immunity function impairment induced by isoproterenol. The results indicated that quercetin possesses activity against isoproterenol-induced myocardial oxidative injury and immunity function impairment, and that the mechanism of pharmacological action was related at least in part to the antioxidant activity of quercetin. Full article

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Anti-inflammatory Activity of Hautriwaic Acid Isolated from Dodonaea viscosa Leaves

by David Osvaldo Salinas-Sánchez, Maribel Herrera-Ruiz, Salud Pérez, Enrique Jiménez-Ferrer and Alejandro Zamilpa

Molecules 2012, 17(4), 4292-4299; https://doi.org/10.3390/molecules17044292 - 10 Apr 2012

Cited by 37 | Viewed by 8379

Abstract

The aim of this study was to identify an anti-inflammatory compound from D. viscosa leaves. The structure of this bioactive substance was elucidated by IR and NMR studies, which indicated that this natural product corresponds to hautriwaic acid (HA). This diterpene exhibited good [...] Read more.

The aim of this study was to identify an anti-inflammatory compound from D. viscosa leaves. The structure of this bioactive substance was elucidated by IR and NMR studies, which indicated that this natural product corresponds to hautriwaic acid (HA). This diterpene exhibited good anti-inflammatory activity in 12-O-tetradecanoylphorbol 13-acetate (TPA) mice ear edema models by applications at doses of 0.25, 0.5 and 1.0 mg/ear (60.2, 70.2 and 87.1% inhibition, respectively); additionally Dodonaea viscosa dichloro-methane extract (DvDE) displays a 97.8% anti-inflammatory effect at 3 mg/kg. Multiple applications of DvDE at doses of 100 mg/kg on TPA mice ear edema inhibited the edema-associated inflammation by 71.8%, while HA at doses of 15 mg/kg, reduced edema to 64% and indomethacin 40%. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Organocatalysis in Synthesis: L-Proline as an Enantioselective Catalyst in the Synthesis of Pyrans and Thiopyrans

by Noha M. Hilmy Elnagdi and Noura Saad Al-Hokbany

Molecules 2012, 17(4), 4300-4312; https://doi.org/10.3390/molecules17044300 - 10 Apr 2012

Cited by 78 | Viewed by 11941

Abstract

The multicomponent reaction (MCR) of aromatic aldehydes 1 and malononitrile (2) with active methylenes 5a–h in the presence of L-proline produced pyrans and thiopyrans 6a–h stereospecifically and in good yields. Moreover a novel MCR of ethyl propiolate [...] Read more.

The multicomponent reaction (MCR) of aromatic aldehydes 1 and malononitrile (2) with active methylenes 5a–h in the presence of L-proline produced pyrans and thiopyrans 6a–h stereospecifically and in good yields. Moreover a novel MCR of ethyl propiolate (8) with 1 and 2 in the presence of L-proline to afford (R)-polysubstituted pyran is also reported. X-ray structures, e.e. and optical activity of the synthesized compounds indicated that L-proline as a catalyst is responsible for the observed enantioselectivity in the studied reactions. Full article

(This article belongs to the Special Issue Organocatalysis)

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Open AccessCommunication

New Methodology for the Synthesis of Thiobarbiturates Mediated by Manganese(III) Acetate

by Ahlem Bouhlel, Christophe Curti and Patrice Vanelle

Molecules 2012, 17(4), 4313-4325; https://doi.org/10.3390/molecules17044313 - 10 Apr 2012

Cited by 9 | Viewed by 7434

Abstract

A three step synthesis of various thiobarbiturate derivatives 17–24 was established. The first step is mediated by Mn(OAc)₃, in order to generate a carbon-carbon bond between a terminal alkene and malonate. Derivatives 1–8 were obtained in moderate [...] Read more.

A three step synthesis of various thiobarbiturate derivatives 17–24 was established. The first step is mediated by Mn(OAc)₃, in order to generate a carbon-carbon bond between a terminal alkene and malonate. Derivatives 1–8 were obtained in moderate to good yields under mild conditions. This key step allows synthesis of a wide variety of lipophilic thiobarbiturates, which could be tested for their anticonvulsive or anesthesic potential. Full article

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Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

by Adlin Afzan, Noor Rain Abdullah, Siti Zaleha Halim, Badrul Amini Rashid, Raja Hazlini Raja Semail, Noordini Abdullah, Ibrahim Jantan, Hussin Muhammad and Zakiah Ismail

Molecules 2012, 17(4), 4326-4342; https://doi.org/10.3390/molecules17044326 - 10 Apr 2012

Cited by 65 | Viewed by 15536

Abstract

Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the [...] Read more.

Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Synthesis and Calcium Mobilization Activity of cADPR Analogues Which Integrate Nucleobase, Northern and Southern Ribose Modifications

by Yue Zhou, Peilin Yu, Hongwei Jin, Zhenjun Yang, Jianbo Yue, Liangren Zhang and Lihe Zhang

Molecules 2012, 17(4), 4343-4356; https://doi.org/10.3390/molecules17044343 - 10 Apr 2012

Cited by 8 | Viewed by 7432

Abstract

Novel cADPR mimics, which integrate nucleobase, northern and southern ribose modifications were synthesized. The key steps of the synthesis were a Cu(I)-catalyzed Hüisgen [3+2] cycloaddition and a microwave-assisted intramolecular pyrophosphorylation. Preliminary biological investigations showed that these cADPR mimics are membrane-permeating agonists of the [...] Read more.

Novel cADPR mimics, which integrate nucleobase, northern and southern ribose modifications were synthesized. The key steps of the synthesis were a Cu(I)-catalyzed Hüisgen [3+2] cycloaddition and a microwave-assisted intramolecular pyrophosphorylation. Preliminary biological investigations showed that these cADPR mimics are membrane-permeating agonists of the calcium signaling pathway. The introduction of chlorine or fluorine at the 2'-position of the southern riboses led to a decrease of activity. The existence of a hydrophobic group on the 3'-OH of the southern riboses does not obviously alter the agonistic activity. Full article

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Open AccessArticle

Bio-Functional Constituents from the Stems of Liriodendron tulipifera

by Chien-Chih Chiu, Han-Lin Chou, Pei-Fang Wu, Hsin-Liang Chen, Hui-Min Wang and Chung-Yi Chen

Molecules 2012, 17(4), 4357-4372; https://doi.org/10.3390/molecules17044357 - 10 Apr 2012

Cited by 32 | Viewed by 8797

Abstract

Four known compounds have been isolated from the stems of Liriodendron tulipifera, and the structures of these pure constituents were determined using spectroscopic analysis. Isolated compounds were screened for free radical scavenging ability, metal chelating power assay and ferric reducing antioxidant power [...] Read more.

Four known compounds have been isolated from the stems of Liriodendron tulipifera, and the structures of these pure constituents were determined using spectroscopic analysis. Isolated compounds were screened for free radical scavenging ability, metal chelating power assay and ferric reducing antioxidant power assay (FRAP). The anti-tyrosinase effects of L. tulipifera compounds were calculated the inhibition of hydroxylation of L-tyrosine to L-dopa according to an in vitro mushroom tyrosinase assay. The study also examined the bio-effects of the four compounds on the human melanoma A375.S2, and showed that liriodenine (1) and (-)-norglaucine (4) significantly inhibited the proliferation of melanoma cells in the cell viability assay. Wound healing results indicated that liriodenine (1), (-)-glaucine (3) and (-)-norglaucine (4) exerted anti-migration potential. Interestingly, (-)-glaucine (3), neither liriodenine (1) nor (-)-norglaucine (4) showed promising anti-migration potential without inducing significant cytotoxicity. Furthermore, a dramatically increased level of intracellular reactive oxygen species (ROS) was detected from (-)-glaucine (3). The cell cycle assessment demonstrated a moderate G2/M accumulation by (-)-glaucine (3). The above results revealed the anti-cancer effects of L. tulipifera compounds, especially on the anti-migration ability indicating the promising chemopreventive agents to human skin melanoma cells. Full article

(This article belongs to the Special Issue Aporphines and Their Oxidized Derivatives: Synthesis and Pharmacological Behavior)

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Open AccessArticle

Chemical Characteristics and Antioxidant Properties of Crude Water Soluble Polysaccharides from Four Common Edible Mushrooms

by Jin-Zhe He, Qiao-Mei Ru, Dan-Dan Dong and Pei-Long Sun

Molecules 2012, 17(4), 4373-4387; https://doi.org/10.3390/molecules17044373 - 11 Apr 2012

Cited by 82 | Viewed by 10303

Abstract

Four crude water soluble polysaccharides, CABP, CAAP, CFVP and CLDP, were isolated from common edible mushrooms, including Agaricus bisporus, Auricularia auricula, Flammulina velutipes and Lentinus edodes, and their chemical characteristics and antioxidant properties were determined. Fourier Transform-infrared analysis showed that [...] Read more.

Four crude water soluble polysaccharides, CABP, CAAP, CFVP and CLDP, were isolated from common edible mushrooms, including Agaricus bisporus, Auricularia auricula, Flammulina velutipes and Lentinus edodes, and their chemical characteristics and antioxidant properties were determined. Fourier Transform-infrared analysis showed that the four crude polysaccharides were all composed of β-glycoside linkages. The major monosaccharide compositions were D-galactose, D-glucose and D-mannose for CABP, CAAP and CLDP, while CFVP was found to consist of L-arabinose, D-galactose, D-glucose and D-mannose. The main molecular weight distributions of CABP and the other three polysaccharides were 66.0 × 10⁴ Da, respectively. Antioxidant properties of the four polysaccharides were evaluated in in vitro systems and CABP showed the best antioxidant properties. The studied mushroom species could potentially be used in part of well-balanced diets and as a source of antioxidant compounds. Full article

(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)

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Open AccessArticle

Adsorption Behavior of Fe(II) and Fe(III) Ions on Thiourea Cross-Linked Chitosan with Fe(III) as Template

by Jun Dai, FengLian Ren and ChunYuan Tao

Molecules 2012, 17(4), 4388-4399; https://doi.org/10.3390/molecules17044388 - 11 Apr 2012

Cited by 47 | Viewed by 8306

Abstract

A new type of thiourea cross-linked chitosan with Fe(III) as template (TCCTS template) was synthesized. The adsorption of Fe(II) and Fe(III) on this TCCTS template was studied. The factors affecting adsorption such as pH and contact time were considered. The results showed that [...] Read more.

A new type of thiourea cross-linked chitosan with Fe(III) as template (TCCTS template) was synthesized. The adsorption of Fe(II) and Fe(III) on this TCCTS template was studied. The factors affecting adsorption such as pH and contact time were considered. The results showed that the optimum pH value for adsorption was pH = 5.0 and the adsorption equilibrium time was about 60 min. The adsorption isotherms and kinetics were investigated, and the equilibrium data agreed very well with the Langmuir model and the pseudo second-order model could describe adsorption process better than the pseudo first-order model. Results also showed that TCCTS template was a favourable adsorbent for Fe(II) and Fe(III) in aqueous solution. Full article

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Open AccessArticle

Assessment of Worldwide Genetic Diversity of Siberian Wild Rye (Elymus sibiricus L.) Germplasm Based on Gliadin Analysis

by Xiao Ma, Shiyong Chen, Xinquan Zhang, Shiqie Bai and Changbing Zhang

Molecules 2012, 17(4), 4424-4434; https://doi.org/10.3390/molecules17044424 - 12 Apr 2012

Cited by 27 | Viewed by 9201

Abstract

E. sibiricus L., the type species of the genus Elymus, is a perennial, self-pollinating and allotetraploid grass indigenous to Northern Asia, which in some countries can be cultivated as an important forage grass. In the present study, eighty-six Elymus sibiricus accessions, mostly [...] Read more.

E. sibiricus L., the type species of the genus Elymus, is a perennial, self-pollinating and allotetraploid grass indigenous to Northern Asia, which in some countries can be cultivated as an important forage grass. In the present study, eighty-six Elymus sibiricus accessions, mostly from different parts of Asia, were assayed by gliadin markers based on Acid Polyacrylamide Gel Electrophoresis to differentiate and explore their genetic relationships. The genetic similarity matrix was calculated by 47 polymorphic bands, which ranged from 0.108 to 0.952 with an average of 0.373. The total Shannon diversity index (H_o) and the Simpson index (H_e) was 0.460 and 0.302, respectively. Cluster analysis showed a clear demarcation between accessions from Qinghai-Tibetan Plateau, China and the others as separate groups. The clustering pattern was probably dependent on geographic origin and ecological adaptability of the accessions. The population structure analysis based on Shannon indices showed that the proportion of variance within and among the five geographic regions of the Northern Hemisphere was 55.9 and 44.1%, respectively, or 63.4 and 36.6% within and among six Chinese provinces. This distinct geographical divergence was perhaps depended on ecogeographical conditions such as climate difference and mountain distribution. The results of gladin analysis in this study are useful for the collection and preservation of E. sibiricus germplasm resources. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessArticle

Investigation on the Protective Effects of Cranberry Against the DNA Damage Induced by Benzo[a]pyrene

by Eduardo Madrigal-Santillán, Sonia Fragoso-Antonio, Carmen Valadez-Vega, Gloria Solano-Solano, Clara Zúñiga Pérez, Manuel Sánchez-Gutiérrez, Jeannett A. Izquierdo-Vega, José Gutiérrez-Salinas, Jaime Esquivel-Soto, César Esquivel-Chirino, Teresa Sumaya-Martínez, Tomas Fregoso-Aguilar, Jorge Mendoza-Pérez and José A. Morales-González

Molecules 2012, 17(4), 4435-4451; https://doi.org/10.3390/molecules17044435 - 12 Apr 2012

Cited by 13 | Viewed by 6750

Abstract

There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is [...] Read more.

There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition. Full article

284 KiB

Open AccessCommunication

Selective Formation of Twisted Intramolecular Charge Transfer and Excimer Emissions on 2,7-bis(4-Diethylaminophenyl)-fluorenone by Choice of Solvent

by Masayuki Shigeta, Mifumi Morita and Gen-ichi Konishi

Molecules 2012, 17(4), 4452-4459; https://doi.org/10.3390/molecules17044452 - 13 Apr 2012

Cited by 28 | Viewed by 8066

Abstract

We designed and synthesized a donor-acceptor-donor dye consisting of a 2,7-disubstituted fluorenone with diethylaminophenyl moieties present as strong electron donating groups. Switching between twisted intramolecular charge transfer (TICT) emission and excimer emission was achieved, with no ground state changes, by simply changing the [...] Read more.

We designed and synthesized a donor-acceptor-donor dye consisting of a 2,7-disubstituted fluorenone with diethylaminophenyl moieties present as strong electron donating groups. Switching between twisted intramolecular charge transfer (TICT) emission and excimer emission was achieved, with no ground state changes, by simply changing the solvent used. In a nonpolar solvent, excimer emission was observed; with increasing polarity, the emission gradually disappeared, and the TICT emission appeared. Full article

(This article belongs to the Special Issue Fluorophores - The Fluorescent Toolbox in Biological and Biomedical Research)

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571 KiB

Open AccessArticle

Synthesis of 2RS,4RS-1-[2-Phenyl-4-[2-(2-trifluromethoxy-phenoxy)-ethyl]-1,3-dioxolan-2-yl-methyl]-1H-1,2,4-triazole Derivatives as Potent Inhibitors of Brassinosteroid Biosynthesis

by Kazuhiro Yamada, Yuko Yoshizawa and Keimei Oh

Molecules 2012, 17(4), 4460-4473; https://doi.org/10.3390/molecules17044460 - 13 Apr 2012

Cited by 22 | Viewed by 8644

Abstract

Brassinosteroids are important phytohormones that affect many aspects of plant growth and development. In order to manipulate brassinosteroid levels in plant tissues by using specific biosynthesis inhibitors, we have carried out a systemic search for specific inhibitors of brassinosteroid biosynthesis. Synthesis of triazole [...] Read more.

Brassinosteroids are important phytohormones that affect many aspects of plant growth and development. In order to manipulate brassinosteroid levels in plant tissues by using specific biosynthesis inhibitors, we have carried out a systemic search for specific inhibitors of brassinosteroid biosynthesis. Synthesis of triazole derivatives based on the ketoconazole scaffold revealed a series of novel brassinosteroid biosynthesis inhibitors (the YCZ series). To explore the structure-activity relationships of this synthetic series, we now report the synthesis of new triazole derivatives with different aromatic structures at position 2 of 1,3-dioxolane skeleton. We found that the variation of aromatic substituent significantly affect the inhibitory potency. Structure-activity relationships studies indicated that 4-chlorophenyl analogue is the most potent inhibitor of BR biosynthesis with an IC₅₀ value approximately 0.12 ± 0.04 µM, while a bulky biphenyl group exhibited a great negative effect on promoting the inhibitory potency with an IC₅₀ larger than 10 µM. Full article

(This article belongs to the Collection Bioactive Compounds)

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342 KiB

Open AccessArticle

Antiangiogenic Polyketides from Peperomia dindygulensis Miq.

by Qi-Wei Wang, De-Hong Yu, Meng-Gan Lin, Mei Zhao, Wen-Jun Zhu, Qin Lu, Gui-Xiu Li, Chao Wang, Yi-Fang Yang, Xue-Mei Qin, Chao Fang, Hong-Zhuan Chen and Guo-Hong Yang

Molecules 2012, 17(4), 4474-4483; https://doi.org/10.3390/molecules17044474 - 13 Apr 2012

Cited by 27 | Viewed by 9236

Abstract

Two new polyketides: 2Z-(heptadec-12-enyl)-4-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (1) and 2-(heptadec-12-enyl)-5-hydroxy-5,6,7,8-tetrahydrochromen- 4-one (2), together with eleven known compounds: 4-hydroxy-2-[(3,4-methylenedioxy- phenyl)tridecanoyl] cyclohexane-1,3-dione (3), oleiferinone (4), 4-hydroxy-2-[(3,4- methylenedioxyphenyl)undecanoyl]cyclohexane-1,3-dione (5), 4-hydroxy-2-[(11-phenyl- undecanoyl)cyclohexane-1,3-dione (6 [...] Read more.

Two new polyketides: 2Z-(heptadec-12-enyl)-4-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one (1) and 2-(heptadec-12-enyl)-5-hydroxy-5,6,7,8-tetrahydrochromen- 4-one (2), together with eleven known compounds: 4-hydroxy-2-[(3,4-methylenedioxy- phenyl)tridecanoyl] cyclohexane-1,3-dione (3), oleiferinone (4), 4-hydroxy-2-[(3,4- methylenedioxyphenyl)undecanoyl]cyclohexane-1,3-dione (5), 4-hydroxy-2-[(11-phenyl- undecanoyl)cyclohexane-1,3-dione (6), proctorione C (7), surinone C (8), 5-hydroxy- 7,8,4'-trimethoxyflavone (9), 5-hydroxy-7,8,3',4'-tetramethoxyflavone (10), 5-hydroxy- 7,3',4'-trimethoxyflavone (11), 5,8-dihydroxy-7,3',4'-trimethoxyflavone (12) and cepharanone B (13) were isolated from the whole plant of Peperomia dindygulensis Miq. Their structures were elucidated by spectroscopic methods, including 2D-NMR techniques. Compounds 2, 3, 5 and 8 inhibited human umbilical vein endothelial cell (HUVEC) proliferation and compounds 5 and 8 sharply suppressed HUVEC tube formation. Full article

(This article belongs to the Section Natural Products Chemistry)

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746 KiB

Open AccessArticle

Natural Chlorophyll-Related Porphyrins and Chlorins for Dye-Sensitized Solar Cells

by Xiao-Feng Wang and Osamu Kitao

Molecules 2012, 17(4), 4484-4497; https://doi.org/10.3390/molecules17044484 - 13 Apr 2012

Cited by 56 | Viewed by 11801

Abstract

Natural-chlorophyll-related porphyrins, including (2H, Zn, Cu)-protoporphyrin IX (Por-1) and Zn-mesoporphyrin IX (Por-2), and chlorins, including chlorin e₆ (Chl-1), chlorin e₄ (Chl-2), and rhodin G₇ (Chl-3), have been used in dye-sensitized solar cells (DSSCs). For porphyrin sensitizers that have vinyl groups [...] Read more.

Natural-chlorophyll-related porphyrins, including (2H, Zn, Cu)-protoporphyrin IX (Por-1) and Zn-mesoporphyrin IX (Por-2), and chlorins, including chlorin e₆ (Chl-1), chlorin e₄ (Chl-2), and rhodin G₇ (Chl-3), have been used in dye-sensitized solar cells (DSSCs). For porphyrin sensitizers that have vinyl groups at the β-positions, zinc coordinated Por-1 gives the highest solar-energy-to-electricity conversion efficiency (h) of up to 2.9%. Replacing the vinyl groups of ZnPor-1 with ethyl groups increases the open-circuit voltage (V_oc) from 0.61 V to 0.66 V, but decreases the short-circuit current (J_sc) from 7.0 mA·cm⁻² to 6.1 mA·cm⁻² and the value of h to 2.8%. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations suggest that the higher J_sc values of Zn-based porphyrin sensitizers result from the favorable electron injection from the LUMO at higher energy levels. In the case of the chlorin sensitizers, the number of carboxyl protons has a large effect on the photovoltaic performance. Chl-2 with two carboxyl protons gives much higher values of J_sc, V_oc, and h than does Chl-1 with three carboxyl protons. Replacing the protons of Chl-1 with sodium ions can substantially improve the photovoltaic performance of Chl-1-based solar cells. Furthermore, the sodium salt of Chl-3 with an aldehyde group at the C7 position shows poorer photovoltaic performance than does the sodium salt of Chl-1 with methyl groups at the C7 position. This is due to the low light-harvesting capability of Chl-3. Full article

(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)

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279 KiB

Open AccessArticle

Regioselectivity in the Ring Opening of Epoxides for the Synthesis of Aminocyclitols from D-(-)-Quinic Acid

by Tzenge-Lien Shih and Shu-Yu Yang

Molecules 2012, 17(4), 4498-4507; https://doi.org/10.3390/molecules17044498 - 16 Apr 2012

Cited by 10 | Viewed by 7039

Abstract

Efficient syntheses of four aminocyclitols are reported. Each synthesis is accomplished in eight steps starting from D-(-)-quinic acid. The key step involves a highly regioselective ring opening of epoxides by sodium azide. Full article

(This article belongs to the Section Organic Chemistry)

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267 KiB

Open AccessArticle

The Suzuki Reaction Applied to the Synthesis of Novel Pyrrolyl and Thiophenyl Indazoles

by Antonella Migliorini, Chiara Oliviero, Tecla Gasperi and Maria Antonietta Loreto

Molecules 2012, 17(4), 4508-4521; https://doi.org/10.3390/molecules17044508 - 16 Apr 2012

Cited by 18 | Viewed by 8409

Abstract

The paper describes the Suzuki cross-coupling of a variety of N and C-3 substituted 5-bromoindazoles with N-Boc-2-pyrrole and 2-thiopheneboronic acids. The reactions, performed in the presence of K₂CO₃, dimethoxyethane and Pd(dppf)Cl₂ as catalyst, gave the corresponding [...] Read more.

The paper describes the Suzuki cross-coupling of a variety of N and C-3 substituted 5-bromoindazoles with N-Boc-2-pyrrole and 2-thiopheneboronic acids. The reactions, performed in the presence of K₂CO₃, dimethoxyethane and Pd(dppf)Cl₂ as catalyst, gave the corresponding adducts in good yields. The methodology allows the facile production of indazole-based heteroaryl compounds, a unique architectural motif that is ubiquitous in biologically active molecules. Full article

(This article belongs to the Section Organic Chemistry)

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752 KiB

Open AccessArticle

Gene Cloning, Expression and Activity Analysis of Manganese Superoxide Dismutase from Two Strains of Gracilaria lemaneiformis (Gracilariaceae, Rhodophyta) under Heat Stress

by Ning Lu, Xiaonan Zang, Xuecheng Zhang, Hao Chen, Xiaoting Feng and Lu Zhang

Molecules 2012, 17(4), 4522-4532; https://doi.org/10.3390/molecules17044522 - 16 Apr 2012

Cited by 17 | Viewed by 6602

Abstract

Manganese superoxide dismutase (Mn-SOD) plays a crucial role in antioxidant responses to environmental stress. To determine whether Mn-SOD affects heat resistance of Gracilaria lemaneiformis, we cloned Mn-SOD cDNA sequences of two strains of this red alga, wild type and cultivar 981. Both [...] Read more.

Manganese superoxide dismutase (Mn-SOD) plays a crucial role in antioxidant responses to environmental stress. To determine whether Mn-SOD affects heat resistance of Gracilaria lemaneiformis, we cloned Mn-SOD cDNA sequences of two strains of this red alga, wild type and cultivar 981. Both cDNA sequences contained an ORF of 675 bp encoding 224 amino acid residues. The cDNA sequences and the deduced amino acid sequences of the two strains shared relatively high identity (more than 99%). No intron existed in genomic DNA of Mn-SOD in G. lemaneiformis. Southern blotting indicated that there were multiple copies, possibly four, of Mn-SOD in both strains. Both in the wild type and cultivar 981, SOD mRNA transcription and SOD activity increased under high temperature stress, while cultivar 981 was more heat resistant based on its SOD activity. This research suggests that there may be a direct relationship between SOD activity and the heat resistance of G. lemaneiformis. Full article

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232 KiB

Open AccessArticle

Large-Scale Solvent-Free Chlorination of Hydroxy-Pyrimidines, -Pyridines, -Pyrazines and -Amides Using Equimolar POCl₃

by Han Wang, Kun Wen, Le Wang, Ye Xiang, Xiaocheng Xu, Yongjia Shen and Zhihua Sun

Molecules 2012, 17(4), 4533-4544; https://doi.org/10.3390/molecules17044533 - 16 Apr 2012

Cited by 22 | Viewed by 19653

Abstract

Chlorination with equimolar POCl₃ can be efficiently achieved not only for hydroxypyrimidines, but also for many other substrates such as 2-hydroxy-pyridines, -quinoxalines, or even -amides. The procedure is solvent-free and involves heating in a sealed reactor at high temperatures using one equivalent [...] Read more.

Chlorination with equimolar POCl₃ can be efficiently achieved not only for hydroxypyrimidines, but also for many other substrates such as 2-hydroxy-pyridines, -quinoxalines, or even -amides. The procedure is solvent-free and involves heating in a sealed reactor at high temperatures using one equivalent of pyridine as base. It is suitable for large scale (multigram) batch preparations. Full article

(This article belongs to the Special Issue Solvent-Free Synthesis)

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321 KiB

Open AccessArticle

Systematic Evaluation of Structure-Activity Relationships of the Riminophenazine Class and Discovery of a C2 Pyridylamino Series for the Treatment of Multidrug-Resistant Tuberculosis

by Binna Liu, Kai Liu, Yu Lu, Dongfeng Zhang, Tianming Yang, Xuan Li, Chen Ma, Meiqin Zheng, Bin Wang, Gang Zhang, Fei Wang, Zhenkun Ma, Chun Li, Haihong Huang and Dali Yin

Molecules 2012, 17(4), 4545-4559; https://doi.org/10.3390/molecules17044545 - 17 Apr 2012

Cited by 24 | Viewed by 10420

Abstract

Clofazimine, a member of the riminophenazine class of drugs, is the cornerstone agent for the treatment of leprosy. This agent is currently being studied in clinical trials for the treatment of multidrug-resistant tuberculosis to address the urgent need for new drugs that can [...] Read more.

Clofazimine, a member of the riminophenazine class of drugs, is the cornerstone agent for the treatment of leprosy. This agent is currently being studied in clinical trials for the treatment of multidrug-resistant tuberculosis to address the urgent need for new drugs that can overcome existing and emerging drug resistance. However, the use of clofazimine in tuberculosis treatment is hampered by its high lipophilicity and skin pigmentation side effects. To identify a new generation of riminophenazines that is less lipophilic and skin staining, while maintaining efficacy, we have performed a systematic structure-activity relationship (SAR) investigation by synthesizing a variety of analogs of clofazimine and evaluating their anti-tuberculosis activity. The study reveals that the central tricyclic phenazine system and the pendant aromatic rings are important for anti-tuberculosis activity. However, the phenyl groups attached to the C2 and N5 position of clofazimine can be replaced by a pyridyl group to provide analogs with improved physicochemical properties and pharmacokinetic characteristics. Replacement of the phenyl group attached to the C2 position by a pyridyl group has led to a promising new series of compounds with improved physicochemical properties, improved anti-tuberculosis potency, and reduced pigmentation potential. Full article

(This article belongs to the Section Medicinal Chemistry)

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603 KiB

Open AccessArticle

A Support Vector Machine Classification Model for Benzo[c]phenathridine Analogues with Topoisomerase-I Inhibitory Activity

by Khac-Minh Thai, Thuy-Quyen Nguyen, Trieu-Du Ngo, Thanh-Dao Tran and Thi-Ngoc-Phuong Huynh

Molecules 2012, 17(4), 4560-4582; https://doi.org/10.3390/molecules17044560 - 17 Apr 2012

Cited by 5 | Viewed by 9776

Abstract

Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, a support vector machine model was performed on a series of 73 analogues to classify BCP derivatives according to TOP-I inhibitory activity. The [...] Read more.

Benzo[c]phenanthridine (BCP) derivatives were identified as topoisomerase I (TOP-I) targeting agents with pronounced antitumor activity. In this study, a support vector machine model was performed on a series of 73 analogues to classify BCP derivatives according to TOP-I inhibitory activity. The best SVM model with total accuracy of 93% for training set was achieved using a set of 7 descriptors identified from a large set via a random forest algorithm. Overall accuracy of up to 87% and a Matthews coefficient correlation (MCC) of 0.71 were obtained after this SVM classifier was validated internally by a test set of 15 compounds. For two external test sets, 89% and 80% BCP compounds, respectively, were correctly predicted. The results indicated that our SVM model could be used as the filter for designing new BCP compounds with higher TOP-I inhibitory activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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506 KiB

Open AccessArticle

Isolation and Identification of Myo-Inositol Crystals from Dragon Fruit (Hylocereus polyrhizus)

by Ow Phui San Rebecca, Amru Nasrulhaq Boyce and Chandran Somasundram

Molecules 2012, 17(4), 4583-4594; https://doi.org/10.3390/molecules17044583 - 17 Apr 2012

Cited by 21 | Viewed by 11927

Abstract

Crystals isolated from Hylocereus polyrhizus were analyzed using four different approaches—X-ray Crystallography, High Performance Liquid Chromatography (HPLC), Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and Nuclear Magnetic Resonance (NMR) and identified as myo-inositol. The X-ray crystallography analysis showed that the unit-cell parameters were: [...] Read more.

Crystals isolated from Hylocereus polyrhizus were analyzed using four different approaches—X-ray Crystallography, High Performance Liquid Chromatography (HPLC), Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and Nuclear Magnetic Resonance (NMR) and identified as myo-inositol. The X-ray crystallography analysis showed that the unit-cell parameters were: a = 6.6226 (3) Å, b = 12.0462 (5) Å, c = 18.8942 (8) Å, α = 90.00, β = 93.98, δ = 90.00. The purity of the crystals were checked using HPLC, whereupon a clean single peak was obtained at 4.8 min with a peak area of 41232 μV*s. The LC-MS/MS technique, which is highly sensitive and selective, was used to provide a comparison of the isolated crystals with a myo-inositol standard where the results gave an identical match for both precursor and product ions. NMR was employed to confirm the molecular structure and conformation of the crystals, and the results were in agreement with the earlier results in this study. The discovery of myo-inositol crystals in substantial amount in H. polyrhizus has thus far not been reported and this is an important finding which will increase the marketability and importance of H. polyrhizus as a crop with a wide array of health properties. Full article

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219 KiB

Open AccessArticle

A New Isorhamnetin Glycoside and Other Phenolic Compounds from Callianthemum taipaicum

by Dong-Mei Wang, Wen-Jun Pu, Yong-Hong Wang, Yu-Juan Zhang and Shan-Shan Wang

Molecules 2012, 17(4), 4595-4603; https://doi.org/10.3390/molecules17044595 - 17 Apr 2012

Cited by 54 | Viewed by 9180

Abstract

A new flavonol glycoside together with five known phenolic compounds were isolated from the whole herb of Callianthemum taipaicum. The compounds were identified as isorhamnetin-3-O-α-L-arabinoside-7-O-β-D-glucoside (1), isorhamnetin-3-O-β-D-glucoside (2), dibutyl phthalate (3 [...] Read more.

A new flavonol glycoside together with five known phenolic compounds were isolated from the whole herb of Callianthemum taipaicum. The compounds were identified as isorhamnetin-3-O-α-L-arabinoside-7-O-β-D-glucoside (1), isorhamnetin-3-O-β-D-glucoside (2), dibutyl phthalate (3), (+)-1-hydroxylpinoresinol-4'-β-D-glucoside (4), pinoresinol-4'-O-β-D-glucoside (5) and 2-phenylethyl-β-primeveroside (6). Compound 1 was identified as a new flavonol glycoside. The compound 6 was isolated for the first time as natural product. All compounds were isolated for the first time from the Callianthemum genus. Furthermore, the 2D-NMR data of the four known compounds 2–5 are given for the first time in this paper. All the structures were identified on the basis of detailed spectral analysis. The compounds 1 and 4 exhibited certain antifungal activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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2239 KiB

Open AccessArticle

Extraction and Characterization of Chitin from the Beetle Holotrichia parallela Motschulsky

by Shaofang Liu, Jie Sun, Lina Yu, Chushu Zhang, Jie Bi, Feng Zhu, Mingjing Qu, Chen Jiang and Qingli Yang

Molecules 2012, 17(4), 4604-4611; https://doi.org/10.3390/molecules17044604 - 17 Apr 2012

Cited by 283 | Viewed by 16462

Abstract

Insect chitin was isolated from adult Holotrichia parallela by treatment with 1 M HCl and 1 M NaOH, following by 1% potassium permanganate solution for decolorization. The yield of chitin from this species is 15%. This insect chitin was compared with the commercial [...] Read more.

Insect chitin was isolated from adult Holotrichia parallela by treatment with 1 M HCl and 1 M NaOH, following by 1% potassium permanganate solution for decolorization. The yield of chitin from this species is 15%. This insect chitin was compared with the commercial a-chitin from shrimp, by infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and elemental analysis. Both chitins exhibited similar chemical structures and physicochemical properties. Adult H. parallela is thus a promising alternative source of chitin. Full article

(This article belongs to the Special Issue Natural Polysaccharides: Chemistry, Bioactivity and Analysis)

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262 KiB

Open AccessArticle

Hydrogel of Ketoconazole and PAMAM Dendrimers: Formulation and Antifungal Activity

by Katarzyna Winnicka, Magdalena Wroblewska, Piotr Wieczorek, Pawel Tomasz Sacha and Elzbieta Tryniszewska

Molecules 2012, 17(4), 4612-4624; https://doi.org/10.3390/molecules17044612 - 18 Apr 2012

Cited by 77 | Viewed by 12383

Abstract

Ketoconazole (KET), an imidazole derivative with well-known antifungal properties, is lipophilic and practically insoluble in water, therefore its clinical use has some practical disadvantages. The aim of the present study was to investigate the influence of PAMAM-NH₂ and PAMAM-OH dendrimers generation 2 [...] Read more.

Ketoconazole (KET), an imidazole derivative with well-known antifungal properties, is lipophilic and practically insoluble in water, therefore its clinical use has some practical disadvantages. The aim of the present study was to investigate the influence of PAMAM-NH₂ and PAMAM-OH dendrimers generation 2 and generation 3 on the solubility and antifungal activity of KET and to design and evaluate KET hydrogel with PAMAM dendrimers. It was shown that the surface charge of PAMAM dendrimers strongly affects their influence on the improvement of solubility and antifungal activity of KET. The MIC and MFC values obtained by broth dilution method indicate that PAMAM-NH₂ dendrimers significantly (up to 16-fold) increased the antifungal activity of KET against Candida strains (e.g., in culture Candida albicans 1103059/11 MIC value was 0.008 μg/mL and 0.064 μg/mL, and MFC was 2 μg/mL and 32 μg/mL for KET in 10 mg/mL solution of PAMAM-NH₂ G2 and pure KET, respectively). Antifungal activity of designed KET hydrogel with PAMAM-NH₂ dendrimers measured by the plate diffusion method was definitely higher than pure KET hydrogel and than commercial available product. It was shown that the improvement of solubility and in the consequence the higher KET release from hydrogels seems to be a very significant factor affecting antifungal activity of KET in hydrogels containing PAMAM dendrimers. Full article

(This article belongs to the Special Issue Dendrimers - from Synthesis to Applications)

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Open AccessArticle

An Improved Synthesis of Pentacene: Rapid Access to a Benchmark Organic Semiconductor

by Chandrani Pramanik and Glen P. Miller

Molecules 2012, 17(4), 4625-4633; https://doi.org/10.3390/molecules17044625 - 20 Apr 2012

Cited by 31 | Viewed by 13387

Abstract

Pentacene is an organic semiconductor used in a variety of thin-film organic electronic devices. Although at least six separate syntheses of pentacene are known (two from dihydropentacenes, two from 6,13-pentacenedione and two from 6,13-dihydro-6,13-dihydroxypentacene), none is ideal and several utilize elevated temperatures that [...] Read more.

Pentacene is an organic semiconductor used in a variety of thin-film organic electronic devices. Although at least six separate syntheses of pentacene are known (two from dihydropentacenes, two from 6,13-pentacenedione and two from 6,13-dihydro-6,13-dihydroxypentacene), none is ideal and several utilize elevated temperatures that may facilitate the oxidation of pentacene as it is produced. Here, we present a fast (~2 min of reaction time), simple, high-yielding (≥90%), low temperature synthesis of pentacene from readily available 6,13-dihydro-6,13-dihydroxypentacene. Further, we discuss the mechanism of this highly efficient reaction. With this improved synthesis, researchers gain rapid, affordable access to high purity pentacene in excellent yield and without the need for a time consuming sublimation. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Synthesis and Antibacterial Evaluation of New N-acylhydrazone Derivatives from Dehydroabietic Acid

by Wen Gu, Rongrong Wu, Shilong Qi, Chenhai Gu, Fanjunnan Si and Zhuhui Chen

Molecules 2012, 17(4), 4634-4650; https://doi.org/10.3390/molecules17044634 - 20 Apr 2012

Cited by 44 | Viewed by 8562

Abstract

A series of new N-acylhydrazone derivatives were synthesized in good yields through the reactions of dehydroabietic acid hydrazide with a variety of substituted arylaldehydes. The structures of the synthesized compounds were confirmed by IR, ¹H- and ¹³C-NMR, ESI-MS, elemental analysis [...] Read more.

A series of new N-acylhydrazone derivatives were synthesized in good yields through the reactions of dehydroabietic acid hydrazide with a variety of substituted arylaldehydes. The structures of the synthesized compounds were confirmed by IR, ¹H- and ¹³C-NMR, ESI-MS, elemental analysis and single crystal X-ray diffraction. From the crystal structure of compound 4l, the C=N double bonds of these N-acylhydrazones showed (E)-configuration, while the NMR data of compounds 4a–q indicated the existence of two rotamers for each compound in solution. The target compounds were evaluated for their antibacterial activities against four microbial strains. The result suggested that several compounds exhibited pronounced antibacterial activities. Particularly, compound 4p exhibited good antibacterial activity against Staphylococcus aureus and Bacillus subtilis comparable to positive control. The possible antibacterial metabolism and the strategy for further optimization of this compound were also discussed. Full article

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Open AccessArticle

Anti-Tumour Promoting Activity and Antioxidant Properties of Girinimbine Isolated from the Stem Bark of Murraya koenigii S.

by Yih Yih Kok, Lim Yang Mooi, Kartini Ahmad, Mohd Aspollah Sukari, Nashriyah Mat, Mawardi Rahmani and Abdul Manaf Ali

Molecules 2012, 17(4), 4651-4660; https://doi.org/10.3390/molecules17044651 - 20 Apr 2012

Cited by 45 | Viewed by 8103

Abstract

Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of [...] Read more.

Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV) in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R). However, diffused early antigen (EA-D) was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH)-free radical. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

The Rotational Barrier in Ethane: A Molecular Orbital Study

by Ramiro F. Quijano-Quiñones, Mariana Quesadas-Rojas, Gabriel Cuevas and Gonzalo J. Mena-Rejón

Molecules 2012, 17(4), 4661-4671; https://doi.org/10.3390/molecules17044661 - 20 Apr 2012

Cited by 24 | Viewed by 11741

Abstract

The energy change on each Occupied Molecular Orbital as a function of rotation about the C-C bond in ethane was studied using the B3LYP, mPWB95 functional and MP2 methods with different basis sets.Also, the effect of the ZPE on rotational barrier was analyzed. [...] Read more.

The energy change on each Occupied Molecular Orbital as a function of rotation about the C-C bond in ethane was studied using the B3LYP, mPWB95 functional and MP2 methods with different basis sets.Also, the effect of the ZPE on rotational barrier was analyzed. We have found that σ and π energies contribution stabilize a staggered conformation. The σ_s molecular orbital stabilizes the staggered conformation while the stabilizes the eclipsed conformation and destabilize the staggered conformation. The π_z and molecular orbitals stabilize both the eclipsed and staggered conformations, which are destabilized by the π_v and molecular orbitals. The results show that the method of calculation has the effect of changing the behavior of the energy change in each Occupied Molecular Orbital energy as a function of the angle of rotation about the C–C bond in ethane. Finally, we found that if the molecular orbital energy contribution is deleted from the rotational energy, an inversion in conformational preference occurs. Full article

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Open AccessArticle

Effect of Paeonol on Antioxidant and Immune Regulatory Activity in Hepatocellular Carcinoma Rats

by Bendong Chen, Mingliang Ning and Guangshun Yang

Molecules 2012, 17(4), 4672-4683; https://doi.org/10.3390/molecules17044672 - 20 Apr 2012

Cited by 105 | Viewed by 8428

Abstract

The study investigated the immunity and antioxidant potential of paeonol by employing a hepatocellular carcinoma (HCC) rat model. Three doses of paeonol (20, 40, 60 mg/kg b.w. orally) were administrated to diethylnitrosamine (DEN)-induced HCC rats. Results showed that paeonol significantly reduced the serum [...] Read more.

The study investigated the immunity and antioxidant potential of paeonol by employing a hepatocellular carcinoma (HCC) rat model. Three doses of paeonol (20, 40, 60 mg/kg b.w. orally) were administrated to diethylnitrosamine (DEN)-induced HCC rats. Results showed that paeonol significantly reduced the serum AST, ALT, ALP, GGT, AFU and liver MDA levels, increased serum WBC, TP, ALB, A/G, TNF-α and IFN-γ and liver antioxidant enzymes activities (SOD, CAT, GSH-Px, GR) in HCC rats. Altogether, these results suggest that the paeonol could effectively decrease oxidative injury and improve immunity function in HCC rats. Full article

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Open AccessArticle

Self-Organizing Maps of Molecular Descriptors for Sesquiterpene Lactones and Their Application to the Chemotaxonomy of the Asteraceae Family

by Marcus T. Scotti, Vicente Emerenciano, Marcelo J. P. Ferreira, Luciana Scotti, Ricardo Stefani, Marcelo S. Da Silva and Francisco Jaime B. Mendonça Junior

Molecules 2012, 17(4), 4684-4702; https://doi.org/10.3390/molecules17044684 - 20 Apr 2012

Cited by 37 | Viewed by 9567

Abstract

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered [...] Read more.

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps. Maps that were generated with each descriptor divided the Asteraceae tribes, with total index values between 66.7% and 83.6%. The analysis of the results shows evident similarities among the Heliantheae, Helenieae and Eupatorieae tribes as well as between the Anthemideae and Inuleae tribes. Those observations are in agreement with systematic classifications that were proposed by Bremer, which use mainly morphological and molecular data, therefore chemical markers partially corroborate with these classifications. The results demonstrate that the atom-centred and RDF descriptors can be used as a tool for taxonomic classification in low hierarchical levels, such as tribes. Descriptors obtained through fragments or by the two-dimensional representation of the SL structures were sufficient to obtain significant results, and better results were not achieved by using descriptors derived from three-dimensional representations of SLs. Such models based on physico-chemical properties can project new design SLs, similar structures from literature or even unreported structures in two-dimensional chemical space. Therefore, the generated SOMs can predict the most probable tribe where a biologically active molecule can be found according Bremer classification. Full article

(This article belongs to the Special Issue Terpenoids)

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Open AccessArticle

Synthesis and Cytotoxic Activity of Some Novel N-Pyridinyl-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide Derivatives

by Huaiwei Ding, Zhe Chen, Cunlong Zhang, Tian Xin, Yini Wang, Hongrui Song, Yuyang Jiang, Yuzong Chen, Yongnan Xu and Chunyan Tan

Molecules 2012, 17(4), 4703-4716; https://doi.org/10.3390/molecules17044703 - 23 Apr 2012

Cited by 28 | Viewed by 8244

Abstract

A series of novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (5a), and tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. [...] Read more.

A series of novel compounds bearing imidazo[2,1-b]thiazole scaffolds were designed and synthesized based on the optimization of the virtual screening hit compound N-(6-morpholinopyridin-3-yl)-2-(6-phenylimidazo[2,1-b]thiazol-3-yl)acetamide (5a), and tested for their cytotoxicity against human cancer cell lines, including HepG2 and MDA-MB-231. The results indicated that the compound 2-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl)-N-(6-(4-(4-methoxybenzyl)piperazin-1-yl)pyridin-3-yl)acetamide (5l), with slightly higher inhibition on VEGFR2 than 5a (5.72% and 3.76% inhibitory rate at 20 μM, respectively), was a potential inhibitor against MDA-MB-231 (IC₅₀ = 1.4 μM) compared with sorafenib (IC₅₀ = 5.2 μM), and showed more selectivity against MDA-MB-231 than HepG2 cell line (IC₅₀ = 22.6 μM). Full article

(This article belongs to the Section Medicinal Chemistry)

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549 KiB

Open AccessArticle

Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro-naphthalene (2',3',4',6'-Tetra-O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives

by Maha S. Al-Mutairi, Ebtehal S. Al-Abdullah, Mogedda E. Haiba, Mohammed A. Khedr and Wafaa A. Zaghary

Molecules 2012, 17(4), 4717-4732; https://doi.org/10.3390/molecules17044717 - 23 Apr 2012

Cited by 11 | Viewed by 7253

Abstract

A facile, convenient and high yielding synthesis of novel S-glycosides and N-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons 2, 4, and 7 were coupled with different activated halosugars in the presence of basic and [...] Read more.

A facile, convenient and high yielding synthesis of novel S-glycosides and N-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons 2, 4, and 7 were coupled with different activated halosugars in the presence of basic and acidic medium. The preliminary in-vitro cytotoxic evaluation revealed that compounds 3c, 3f, 5c and 7b show promising activity. A molecular docking study was performed against tyrosine kinase (TK) (PDB code: 1t46) by Autodock Vina. The docking output was analyzed and some compounds have shown hydrogen bond (H-B) formation with reasonable distances ranged from 2.06 A° to 3.06 A° with Thr 670 and Cys 673 residues found in the specified pocket. No hydrogen bond was observed with either Glu 640 nor Asp 810 residues, as was expected from pdbsum. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Simultaneous Determination of Salidroside and Its Aglycone Metabolite p-Tyrosol in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry

by Na Guo, Zhiwei Hu, Xiaoxu Fan, Jian Zheng, Dehui Zhang, Tao Xu, Tao Yu, Yang Wang and Haiying Li

Molecules 2012, 17(4), 4733-4754; https://doi.org/10.3390/molecules17044733 - 23 Apr 2012

Cited by 44 | Viewed by 10699

Abstract

Salidroside and its aglycone p-tyrosol are two major phenols in the genus Rhodiola and have been confirmed to possess various pharmacological properties. In our present study, p-tyrosol was identified as the deglycosylation metabolite of salidroside after intravenous (i.v.) administration to rats [...] Read more.

Salidroside and its aglycone p-tyrosol are two major phenols in the genus Rhodiola and have been confirmed to possess various pharmacological properties. In our present study, p-tyrosol was identified as the deglycosylation metabolite of salidroside after intravenous (i.v.) administration to rats at a dose of 50 mg/kg, but was not detectable after intragastric gavage (i.g.) administration through HPLC-photodiode array detection (PDA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Next, an accurate and precise LC-MS/MS method was developed to quantitatively determine salidroside and p-tyrosol in rat plasma samples. Samples were analyzed by LC-MS/MS on a reverse-phase xTerra MS C18 column which was equilibrated and eluted with an isocratic mixture of acetonitrile-water (1:9, v/v) at a flow rate of 0.3 mL/min. The analytes were monitored by multiple reaction monitoring (MRM) under the negative electrospray ionization mode. The precursor/product transitions (m/z) were 299.0→118.8 for salidroside, 137.0→118.9 for p-tyrosol and 150.1→106.9 for the internal standard (IS), paracetamol, respectively. The calibration curve was linear over the concentration ranges of 50–2,000 ng/mL for salidroside and 20–200 ng/mL for p-tyrosol. The inter- and intra-day accuracy and precision were within ±15%. The method has been successfully applied to the pharmacokinetic study and the oral bioavailability was calculated. Full article

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Review

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Open AccessReview

Chemistry and Biological Activities of Terpenoids from Copaiba (Copaifera spp.) Oleoresins

by Lidiam Maia Leandro, Fabiano De Sousa Vargas, Paula Cristina Souza Barbosa, Jamilly Kelly Oliveira Neves, José Alexsandro Da Silva and Valdir Florêncio Da Veiga-Junior

Molecules 2012, 17(4), 3866-3889; https://doi.org/10.3390/molecules17043866 - 30 Mar 2012

Cited by 188 | Viewed by 26606

Abstract

Copaiba oleoresins are exuded from the trunks of trees of the Copaifera species (Leguminosae-Caesalpinoideae). This oleoresin is a solution of diterpenoids, especially, mono- and di-acids, solubilized by sesquiterpene hydrocarbons. The sesquiterpenes and diterpenes (labdane, clerodane and kaurane skeletons) are different for each Copaifera [...] Read more.

Copaiba oleoresins are exuded from the trunks of trees of the Copaifera species (Leguminosae-Caesalpinoideae). This oleoresin is a solution of diterpenoids, especially, mono- and di-acids, solubilized by sesquiterpene hydrocarbons. The sesquiterpenes and diterpenes (labdane, clerodane and kaurane skeletons) are different for each Copaifera species and have been linked to several reported biological activities, ranging from anti-tumoral to embriotoxic effects. This review presents all the substances already described in this oleoresin, together with structures and activities of its main terpenoids. Full article

(This article belongs to the Special Issue Terpenoids)

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Open AccessReview

Essential Oils in Combination and Their Antimicrobial Properties

by Imaël Henri Nestor Bassolé and H. Rodolfo Juliani

Molecules 2012, 17(4), 3989-4006; https://doi.org/10.3390/molecules17043989 - 2 Apr 2012

Cited by 857 | Viewed by 45819

Abstract

Essential oils (EOs) have been long recognized for their antibacterial, antifungal, antiviral, insecticidal and antioxidant properties. They are widely used in medicine and the food industry for these purposes. The increased interest in alternative natural substances is driving the research community to find [...] Read more.

Essential oils (EOs) have been long recognized for their antibacterial, antifungal, antiviral, insecticidal and antioxidant properties. They are widely used in medicine and the food industry for these purposes. The increased interest in alternative natural substances is driving the research community to find new uses and applications of these substances. EOs and their components show promising activities against many food-borne pathogens and spoilage microorganisms when tested in vitro. In food systems, higher concentrations of EOs are needed to exert similar antibacterial effects as those obtained in in vitro assays. The use of combinations of EOs and their isolated components are thus new approaches to increase the efficacy of EOs in foods, taking advantage of their synergistic and additive effects. The purpose of this review is to provide an overview on the antimicrobial efficacy of these combinations. A survey of the methods used for the determination of the interactions and mechanisms involved in the antimicrobial activities of these combinations are also reported. Full article

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Open AccessReview

Advanced Fluorescence Microscopy Techniques—FRAP, FLIP, FLAP, FRET and FLIM

by Hellen C. Ishikawa-Ankerhold, Richard Ankerhold and Gregor P. C. Drummen

Molecules 2012, 17(4), 4047-4132; https://doi.org/10.3390/molecules17044047 - 2 Apr 2012

Cited by 387 | Viewed by 82330

Abstract

Fluorescence microscopy provides an efficient and unique approach to study fixed and living cells because of its versatility, specificity, and high sensitivity. Fluorescence microscopes can both detect the fluorescence emitted from labeled molecules in biological samples as images or photometric data from which [...] Read more.

Fluorescence microscopy provides an efficient and unique approach to study fixed and living cells because of its versatility, specificity, and high sensitivity. Fluorescence microscopes can both detect the fluorescence emitted from labeled molecules in biological samples as images or photometric data from which intensities and emission spectra can be deduced. By exploiting the characteristics of fluorescence, various techniques have been developed that enable the visualization and analysis of complex dynamic events in cells, organelles, and sub-organelle components within the biological specimen. The techniques described here are fluorescence recovery after photobleaching (FRAP), the related fluorescence loss in photobleaching (FLIP), fluorescence localization after photobleaching (FLAP), Förster or fluorescence resonance energy transfer (FRET) and the different ways how to measure FRET, such as acceptor bleaching, sensitized emission, polarization anisotropy, and fluorescence lifetime imaging microscopy (FLIM). First, a brief introduction into the mechanisms underlying fluorescence as a physical phenomenon and fluorescence, confocal, and multiphoton microscopy is given. Subsequently, these advanced microscopy techniques are introduced in more detail, with a description of how these techniques are performed, what needs to be considered, and what practical advantages they can bring to cell biological research. Full article

(This article belongs to the Special Issue Fluorophores - The Fluorescent Toolbox in Biological and Biomedical Research)

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571 KiB

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Ionic Liquid Applications in Peptide Chemistry: Synthesis, Purification and Analytical Characterization Processes

by Alesia A. Tietze, Pascal Heimer, Annegret Stark and Diana Imhof

Molecules 2012, 17(4), 4158-4185; https://doi.org/10.3390/molecules17044158 - 5 Apr 2012

Cited by 51 | Viewed by 11720

Abstract

This review aims to provide a comprehensive overview of the recent advances made in the field of ionic liquids in peptide chemistry and peptide analytics. Full article

(This article belongs to the Collection Ionic Liquids)

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Open AccessReview

HCN Channels and Heart Rate

by Pietro Scicchitano, Santa Carbonara, Gabriella Ricci, Cosimo Mandurino, Manuela Locorotondo, Gabriella Bulzis, Michele Gesualdo, Annapaola Zito, Rosa Carbonara, Ilaria Dentamaro, Graziano Riccioni and Marco Matteo Ciccone

Molecules 2012, 17(4), 4225-4235; https://doi.org/10.3390/molecules17044225 - 5 Apr 2012

Cited by 38 | Viewed by 11797

Abstract

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the “funny” pacemaker current (I_f), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of [...] Read more.

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the “funny” pacemaker current (I_f), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control. Full article

(This article belongs to the Special Issue Ivabradine)

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257 KiB

Open AccessReview

Honey: A Novel Antioxidant

by Omotayo O. Erejuwa, Siti A. Sulaiman and Mohd S. Ab Wahab

Molecules 2012, 17(4), 4400-4423; https://doi.org/10.3390/molecules17044400 - 12 Apr 2012

Cited by 242 | Viewed by 29367

Abstract

The global prevalence of chronic diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer and Alzheimer's disease is on the rise. These diseases, which constitute the major causes of death globally, are associated with oxidative stress. Oxidative stress is defined as an “imbalance between [...] Read more.

The global prevalence of chronic diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer and Alzheimer's disease is on the rise. These diseases, which constitute the major causes of death globally, are associated with oxidative stress. Oxidative stress is defined as an “imbalance between oxidants and antioxidants in favor of the oxidants, potentially leading to damage”. Individuals with chronic diseases are more susceptible to oxidative stress and damage because they have elevated levels of oxidants and/or reduced antioxidants. This, therefore, necessitates supplementation with antioxidants so as to delay, prevent or remove oxidative damage. Honey is a natural substance with many medicinal effects such as antibacterial, hepatoprotective, hypoglycemic, reproductive, antihypertensive and antioxidant effects. This review presents findings that indicate honey may ameliorate oxidative stress in the gastrointestinal tract (GIT), liver, pancreas, kidney, reproductive organs and plasma/serum. Besides, the review highlights data that demonstrate the synergistic antioxidant effect of honey and antidiabetic drugs in the pancreas, kidney and serum of diabetic rats. These data suggest that honey, administered alone or in combination with conventional therapy, might be a novel antioxidant in the management of chronic diseases commonly associated with oxidative stress. In view of the fact that the majority of these data emanate from animal studies, there is an urgent need to investigate this antioxidant effect of honey in human subjects with chronic or degenerative diseases. Full article

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RETRACTED: Dynamic Action of Carotenoids in Cardioprotection and Maintenance of Cardiac Health

by Mahesh Agarwal, Royapuram P. Parameswari, Hannah R. Vasanthi and Dipak K. Das

Molecules 2012, 17(4), 4755-4769; https://doi.org/10.3390/molecules17044755 - 23 Apr 2012

Cited by 50 | Viewed by 12392 | Retraction

Abstract

Oxidative stress has been considered universally and undeniably implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress activate transcriptional messengers, such as nuclear factor—κB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible [...] Read more.

Oxidative stress has been considered universally and undeniably implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress activate transcriptional messengers, such as nuclear factor—κB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Evidence is rapidly accumulating to support the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as intracellular signaling molecules. Despite this connection between oxidative stress and cardiovascular disease (CVD), there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, “upstream” approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. Short-term dietary intervention trials suggest that diets rich in fruit and vegetable intake lead to improvements in coronary risk factors and reduce cardiovascular mortality. Carotenoids are such abundant, plant-derived, fat-soluble pigments that functions as antioxidants. They are stored in the liver or adipose tissue, and are lipid soluble by becoming incorporated into plasma lipoprotein particles during transport. For these reasons, carotenoids may represent one plausible mechanism by which fruits and vegetables reduce the risk of chronic diseases as cardiovascular disease (CVD). This review paper outlines the role of carotenoids in maintaining cardiac health and cardioprotection mediated by several mechanisms including redox signaling. Full article

(This article belongs to the Special Issue Carotenoids)

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