Molecules

20 pages, 853 KiB

Open AccessCommunication

Electron Transfer-Induced Coupling of Haloarenes to Styrenes and 1,1-Diphenylethenes Triggered by Diketopiperazines and Potassium tert-Butoxide

by Eswararao Doni, Shengze Zhou and John A. Murphy^*

WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK

Molecules 2015, 20(2), 1755-1774; https://doi.org/10.3390/molecules20021755 - 22 Jan 2015

Cited by 30 | Viewed by 11216

Abstract

The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast to previously reported reactions where phenanthroline has been used to mediate the reactions, the use of diketopiperazines can lead [...] Read more.

The coupling of haloarenes to styrenes and 1,1-diarylethenes has been achieved with potassium tert-butoxide in the presence of N,N'-dialkyldiketopiperazines. In contrast to previously reported reactions where phenanthroline has been used to mediate the reactions, the use of diketopiperazines can lead to either 1,1,2-triarylethenes or 1,1,2-triarylethanes, depending on the conditions used. Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

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13 pages, 1598 KiB

Open AccessArticle

A Redox-Controllable Molecular Switch Based on Weak Recognition of BPX26C6 at a Diphenylurea Station

by Jia-Cheng Chang¹, Chien-Chen Lai² and Sheng-Hsien Chiu^1,*

¹ Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan

² Institute of Molecular Biology, National Chung Hsing University, Taichung 402, Taiwan

Molecules 2015, 20(2), 1775-1787; https://doi.org/10.3390/molecules20021775 - 22 Jan 2015

Cited by 2 | Viewed by 8537

Abstract

The Na⁺ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF₄ to oxidize the triarylamine terminus into a corresponding radical cation attracted [...] Read more.

The Na⁺ ion–assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF₄ to oxidize the triarylamine terminus into a corresponding radical cation attracted the macrocyclic component toward its adjacent carbamate station; subsequent addition of Zn powder moved the macrocyclic component back to its urea station. Full article

(This article belongs to the Special Issue Host-Guest Chemistry)

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36 pages, 27563 KiB

Open AccessReview

Lectins: Getting Familiar with Translators of the Sugar Code

by Sabine André¹, Herbert Kaltner¹, Joachim C. Manning¹, Paul V. Murphy²

and Hans-Joachim Gabius^1,*

¹ Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Veterinärstr. 13, 80539 Munich, Germany

² School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland

Molecules 2015, 20(2), 1788-1823; https://doi.org/10.3390/molecules20021788 - 22 Jan 2015

Cited by 90 | Viewed by 12500

Abstract

The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical [...] Read more.

The view on the significance of the presence of glycans in glycoconjugates is undergoing a paradigmatic change. Initially mostly considered to be rather inert and passive, the concept of the sugar code identifies glycans as highly versatile platform to store information. Their chemical properties endow carbohydrates to form oligomers with unsurpassed structural variability. Owing to their capacity to engage in hydrogen (and coordination) bonding and C-H/π-interactions these “code words” can be “read” (in Latin, legere) by specific receptors. A distinct class of carbohydrate-binding proteins are the lectins. More than a dozen protein folds have developed carbohydrate-binding capacity in vertebrates. Taking galectins as an example, distinct expression patterns are traced. The availability of labeled endogenous lectins facilitates monitoring of tissue reactivity, extending the scope of lectin histochemistry beyond that which traditionally involved plant lectins. Presentation of glycan and its cognate lectin can be orchestrated, making a glycan-based effector pathway in growth control of tumor and activated T cells possible. In order to unravel the structural basis of lectin specificity for particular glycoconjugates mimetics of branched glycans and programmable models of cell surfaces are being developed by strategic combination of lectin research with synthetic and supramolecular chemistry. Full article

(This article belongs to the Special Issue Lectins)

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18 pages, 1841 KiB

Open AccessArticle

Synthesis, Bioactivity, Molecular Docking and POM Analyses of Novel Substituted Thieno[2,3-b]thiophenes and Related Congeners

by Yahia N. Mabkhot^1,*

, Fahad D. Aldawsari^2,†, Salim S. Al-Showiman^1,†, Assem Barakat^1,3,*,†

, Taibi Ben Hadda^4,†

, Mohammad S. Mubarak^5,†, Sehrish Naz^6,†, Zaheer Ul-Haq^6,†

and Abdur Rauf^7,†

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

² King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11442, Saudi Arabia

³ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia 21321 Alexandria, Egypt

⁴ Lab of Chemical Material, Faculty of Sciences University Mohammed Premier, Oujda 60000, Morocco

⁵ Department of Chemistry, The University of Jordan, Amman 11942, Jordan

⁶ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75210, Pakistan

⁷ Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 1824-1841; https://doi.org/10.3390/molecules20021824 - 23 Jan 2015

Cited by 25 | Viewed by 8035

Abstract

Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed [...] Read more.

Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed significant activity against both Gram-positive and Gram negative bacteria, in addition to fungi. Molecular docking and POM analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution doesn’t guaranty more efficiency in bioactivity. Full article

(This article belongs to the Section Organic Chemistry)

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18 pages, 775 KiB

Open AccessArticle

Microwave-Assisted Synthesis and Antimicrobial Evaluation of Novel Spiroisoquinoline and Spiropyrido[4,3-d]pyrimidine Derivatives

by Rasha M. Faty¹, Mohamed S. Rashed² and Mohamed M. Youssef^1,*

¹ Chemistry Department, Faculty of Science, Cairo University, Cairo 12613, Egypt

² Schlumberger, Well Services, Al-Khobar 31952, Saudi Arabia

Molecules 2015, 20(2), 1842-1859; https://doi.org/10.3390/molecules20021842 - 23 Jan 2015

Cited by 12 | Viewed by 6143

Abstract

Bromination of N-substituted homophthalimides and tetrahydropyrido[4,3-d]- pyrimidine-5,7-diones produces 4,4-dibromohomophthalimide and 8,8-dibromo-tetrahydropyrido[4,3-d]pyrimidine-5,7-dione derivatives, respectively, that can be used as precursors for spiro derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiroisoquinoline and spirotetrahydropyrido[4,3-d]- [...] Read more.

Bromination of N-substituted homophthalimides and tetrahydropyrido[4,3-d]- pyrimidine-5,7-diones produces 4,4-dibromohomophthalimide and 8,8-dibromo-tetrahydropyrido[4,3-d]pyrimidine-5,7-dione derivatives, respectively, that can be used as precursors for spiro derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiroisoquinoline and spirotetrahydropyrido[4,3-d]- pyrimidine-5,7-dione derivatives, respectively. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro derivatives. All new compounds are prepared by using the usual chemical conditions and microwave assisted conditions. The latter conditions improved the reaction yields, reduced reaction times and ameliorated the effects on the surrounding environment as the reactions are carried out in closed systems. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, MS, ¹H-NMR and ¹³C-NMR and elemental analyses. Some of the newly synthesized compounds were tested for their antimicrobial activities, whereby four of them showed moderate activities and the rest showed low or no activities towards the investigated species. Full article

(This article belongs to the Section Organic Chemistry)

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12 pages, 734 KiB

Open AccessArticle

Antimicrobial and Seasonal Evaluation of the Carvacrol-Chemotype Oil from Lippia origanoides Kunth.

by Sandra Layse F. Sarrazin¹, Leomara Andrade Da Silva², Ana Paula F. De Assunção², Ricardo B. Oliveira², Victor Y. P. Calao², Rodrigo Da Silva², Elena E. Stashenko³, José Guilherme S. Maia^2,4,* and Rosa Helena V. Mourão^1,2,*

¹ Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia Legal, Universidade Federal do Amazonas, 60077-000 Manaus, Brazil

² Programa de Pós-Graduação em Recursos Naturais da Amazônia, Universidade Federal do Oeste do Pará, 68135-110 Santarém, Brazil

³ Chromatography Laboratory, Research Center for Biomolecules, Industrial University of Santander, Bucaramanga 57, Colombia

⁴ Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110 Belém, Brazil

Molecules 2015, 20(2), 1860-1871; https://doi.org/10.3390/molecules20021860 - 23 Jan 2015

Cited by 54 | Viewed by 9019

Abstract

This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the [...] Read more.

This study evaluated the influence of seasonal variation on the yield and composition of essential oil of Lippia origanoides occurring in the Middle Rio Amazonas, Brazil, and the impact on its antimicrobial potential. The average oil yield was 1.7% ± 0.2% in the rainy season and 1.6% ± 0.3% in the dry season. Some correlations with climatic parameters were observed. The major components were carvacrol (rainy, 43.5% ± 1.9%; dry, 41.4% ± 2.04%), thymol (rainy, 10.7% ± 1.1%; dry, 10.6% ± 0.9%), p-cymene (rainy, 9.8% ± 0.7%; dry, 10.0% ± 1.4%) and p-methoxythymol (rainy, 9.6% ± 0.8%; dry, 10.4% ± 1.4%). It was found that the antibacterial activity of L. origanoides against Staphylococcus aureus and Escherichia coli was little influenced by the changes in oil composition due to seasonal variation. Against S. aureus, the oil Minimum Inhibitory Concentration (MIC) value was 1.25 μL/mL over ten months. Against E. coli, the oil MIC values ranged from 0.15 μL/mL to 0.31 μL/mL in different months of the year. The Minimum Bactericidal Concentration (MBC) value was 2.5 μL/mL against S. aureus and 1.25 μL/mL against E. coli. The results suggest that the antimicrobial activity identified in the oil remain unchanged for the full year, allowing its medicinal use without any risk of loss or absence of the active principles of the plant. Full article

(This article belongs to the Collection Bioactive Compounds)

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32 pages, 4756 KiB

Open AccessReview

Natural Products as Leads in Schistosome Drug Discovery

by Bruno J. Neves^1,*, Carolina H. Andrade¹ and Pedro V. L. Cravo²

¹ LabMol—Laboratory for Drug Design and Molecular Modeling, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia 74605-170, Brazil

² GenoBio—Laboratory of Genomics and Biotechnology, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia 74605-050, Brazil

Molecules 2015, 20(2), 1872-1903; https://doi.org/10.3390/molecules20021872 - 23 Jan 2015

Cited by 74 | Viewed by 12038

Abstract

Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating [...] Read more.

Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs) as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS) strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity. Full article

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

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18 pages, 1072 KiB

Open AccessArticle

Ameliorating the Effect of Astragaloside IV on Learning and Memory Deficit after Chronic Cerebral Hypoperfusion in Rats

by Sooyong Kim, Il-Hwan Kang, Jung-Bum Nam, Yoonchul Cho, Doo-Young Chung, Seung-Hwan Kim, Jeong-Soo Kim, Yong-Deok Cho, Eun-Ki Hong, Nak-Won Sohn and Jung-Won Shin^*

Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin 446-701, Korea

Molecules 2015, 20(2), 1904-1921; https://doi.org/10.3390/molecules20021904 - 23 Jan 2015

Cited by 48 | Viewed by 8446

Abstract

Astragaloside IV (AS-IV) has been reported to have a prominent antioxidant effect and was proposed as a promising agent for the prevention of neurodegenerative disorders accompanied by cognitive impairment. The present study investigated the ameliorating effect of AS-IV on learning and memory deficits [...] Read more.

Astragaloside IV (AS-IV) has been reported to have a prominent antioxidant effect and was proposed as a promising agent for the prevention of neurodegenerative disorders accompanied by cognitive impairment. The present study investigated the ameliorating effect of AS-IV on learning and memory deficits induced by chronic cerebral hypoperfusion in rats. Rats were treated with two doses of AS-IV (10 and 20 mg/kg, i.p.) daily for 28 days starting from the 5th week after permanent bilateral common carotid artery occlusion. AS-IV treatment (at dose of 20 mg/kg) significantly improved the spatial learning and memory deficits assessed using the Morris water maze test in rats with chronic cerebral hypoperfusion. AS-IV significantly attenuated neuronal apoptosis as well as the levels of superoxide dismutase and lipid peroxidation markers, including malondialdehyde and 4-hydroxy-2-nonenal, in the hippocampus. AS-IV also significantly reduced 8-hydroxy-2’-deoxyguanosine expression, a maker of oxidative DNA damage, while significantly inhibited the astrocyte and microglia activation in the hippocampus. The results indicate that AS-IV has therapeutic potential for the prevention of dementia caused by cerebral hypoperfusion and suggest that the ameliorating effect of AS-IV on learning and memory deficits might be the result of suppressing neuronal apoptosis and oxidative damage in the hippocampus. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

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19 pages, 717 KiB

Open AccessArticle

Characterization of Four Popular Sweet Cherry Cultivars Grown in Greece by Volatile Compound and Physicochemical Data Analysis and Sensory Evaluation

by Maria V. Vavoura¹, Anastasia V. Badeka¹, Stavros Kontakos² and Michael G. Kontominas^1,3,*

¹ Department of Chemistry, University of Ioannina, 45110-Ioannina, Greece

² Department of Social Administration and Political Science, Democritus University of Thrace, 69100-Komotini, Greece

³ Department of Chemistry, American University in Cairo, 11835-New Cairo, Egypt

Molecules 2015, 20(2), 1922-1940; https://doi.org/10.3390/molecules20021922 - 26 Jan 2015

Cited by 65 | Viewed by 7578

Abstract

Volatile compounds, physicochemical and sensory attributes of four sweet cherry cultivars (Canada giant, Ferrovia, Lapins and Skeena) grown in Northern Greece were determined. Eighteen volatile compounds were identified and semi-quantified in cherries using solid phase micro extraction in combination with gas chromatography/mass spectrometry [...] Read more.

Volatile compounds, physicochemical and sensory attributes of four sweet cherry cultivars (Canada giant, Ferrovia, Lapins and Skeena) grown in Northern Greece were determined. Eighteen volatile compounds were identified and semi-quantified in cherries using solid phase micro extraction in combination with gas chromatography/mass spectrometry (SPME-GC/MS). Carbonyl compounds were the most abundant in sweet cherry aroma, followed by alcohols, esters and hydrocarbons/terpenes. Cherry cultivars in order of increasing amounts of volatiles were: Lapins < Canada giant < Ferrovia < Skeena. Physicochemical parameters determined included: titratable acidity (TA), pH, total soluble solids (TSS), maturity index (MI) and total phenolic content (TPC). TA ranged between 0.21 and 0.28 g malic acid/100 g fresh weight (FW). The pH ranged between 3.81 and 3.96. TSS ranged between 13.00 and 16.00 °Brix. MI ranged between 51.8 and 75.0. TPC ranged between 95.14 and 170.35 mg gallic acid equivalents (GAE)/100 g FW. Sensory evaluation showed that cherry colour, in order of increasing intensity, was: Canada giant < Ferrovia < Lapins < Skeena. Respective order for cherry firmness was: Canada giant < Lapins ≤ Ferrovia < Skeena and for flavour: Lapins < Canada giant < Skeena ≤ Ferrovia. Correlation of volatiles to physicochemical and sensory attributes showed varying trends. Full article

(This article belongs to the Special Issue Aromas and Volatiles of Fruits)

14 pages, 2738 KiB

Open AccessArticle

Visible Light Induced Green Transformation of Primary Amines to Imines Using a Silicate Supported Anatase Photocatalyst

by Sifani Zavahir and Huaiyong Zhu^*

School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane QLD 4001, Australia

Molecules 2015, 20(2), 1941-1954; https://doi.org/10.3390/molecules20021941 - 26 Jan 2015

Cited by 24 | Viewed by 8335

Abstract

Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to [...] Read more.

Catalytic oxidation of amine to imine is of intense present interest since imines are important intermediates for the synthesis of fine chemicals, pharmaceuticals, and agricultural chemicals. However, considerable efforts have been made to develop efficient methods for the oxidation of secondary amines to imines, while little attention has until recently been given to the oxidation of primary amines, presumably owing to the high reactivity of generated imines of primary amines that are easily dehydrogenated to nitriles. Herein, we report the oxidative coupling of a series of primary benzylic amines into corresponding imines with dioxygen as the benign oxidant over composite catalysts of TiO₂ (anatase)-silicate under visible light irradiation of λ > 460 nm. Visible light response of this system is believed to be as a result of high population of defects and contacts between silicate and anatase crystals in the composite and the strong interaction between benzylic amine and the catalyst. It is found that tuning the intensity and wavelength of the light irradiation and the reaction temperature can remarkably enhance the reaction activity. Water can also act as a green medium for the reaction with an excellent selectivity. This report contributes to the use of readily synthesized, environmentally benign, TiO₂ based composite photocatalyst and solar energy to realize the transformation of primary amines to imine compounds. Full article

(This article belongs to the Special Issue Photocatalysis)

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13 pages, 7722 KiB

Open AccessArticle

Purification and Characterization of Chitinases from Ridgetail White Prawn Exopalaemon carinicauda

by Jing Wang^1,2, Jiquan Zhang^1,*, Fengge Song^1,2, Tianshu Gui^1,2 and Jianhai Xiang¹

¹ Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China

² University of Chinese Academy of Sciences, Beijing 100039, China

Molecules 2015, 20(2), 1955-1967; https://doi.org/10.3390/molecules20021955 - 26 Jan 2015

Cited by 30 | Viewed by 8398

Abstract

In this paper, we purified two native chitinases from the hepatopancreas of the ridgetail white prawn Exopalaemon carinicauda by using ion-exchange resin chromatography (IEC) and gel filtration. These two chitinases, named EcChi1 and EcChi2, were identified by chitinolytic activity assay and LC-ESI-MS/MS. Their [...] Read more.

In this paper, we purified two native chitinases from the hepatopancreas of the ridgetail white prawn Exopalaemon carinicauda by using ion-exchange resin chromatography (IEC) and gel filtration. These two chitinases, named EcChi1 and EcChi2, were identified by chitinolytic activity assay and LC-ESI-MS/MS. Their apparent molecular weights were 44 kDa and 65 kDa as determined by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The specific activity of EcChi1 and EcChi2 was 1305.97 U·mg⁻¹ and 28.69 U·mg⁻¹. The optimal temperature and pH of EcChi1 were 37 °C and pH 4.0, respectively. Co²⁺, Fe³⁺, Zn²⁺, Cd²⁺, and Cu²⁺ had an obvious promoting effect upon chitinase activity of EcChi1. For colloidal chitin, the K_m and V_max values of EcChi1 were 2.09 mg·mL⁻¹ and 31.15 U·mL⁻¹·h⁻¹. Full article

(This article belongs to the Collection Advances in Glycosciences)

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16 pages, 1158 KiB

Open AccessCommunication

Synthesis and Biological Evaluation of Novel 6-Hydroxy-benzo[d][1,3]oxathiol-2-one Schiff Bases as Potential Anticancer Agents

by Eliza De Lucas Chazin¹, Paola De Souza Sanches¹, Eric Brazil Lindgren^1,2, Walcimar Trindade Vellasco Júnior^1,3, Laine Celestino Pinto⁴, Rommel Mario Rodríguez Burbano⁴, Julliane Diniz Yoneda⁵, Kátia Zaccur Leal¹, Claudia Regina Brandão Gomes³, James Lewis Wardell^3,6, Solange Maria Silva Veloso Wardell⁷, Raquel Carvalho Montenegro⁴ and Thatyana Rocha Alves Vasconcelos^1,*

¹ Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Batista s/no, Centro, Niterói 24020-141, RJ, Brazil

² School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK

³ Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Farmanguinhos, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil

⁴ Instituto de Ciências Biológicas, Universidade Federal do Pará, Av. Augusto Corrêa 01, Guamá, Belém 66075-110, PA, Brazil

⁵ Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Fluminense, Rua Desembargador Ellis Hemydio Figueira 783, Aterrado, Volta Redonda 27213-415, RJ, Brazil

⁶ Department of Chemistry, University of Aberdeen, Old Aberdeen AB 24 3UE, Scotland

⁷ CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland

Molecules 2015, 20(2), 1968-1983; https://doi.org/10.3390/molecules20021968 - 27 Jan 2015

Cited by 21 | Viewed by 8208

Abstract

With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The [...] Read more.

With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The nitro group of 2 was reduced to give the amino intermediate 3. Schiff bases 4a–r were obtained from coupling reactions between 3 and various benzaldehydes and heteroaromatic aldehydes. All the new compounds were fully identified and characterized by NMR (¹H and ¹³C) and specifically for 4q by X-ray crystallography. The in vitro cytotoxicity of the compounds was evaluated against cancer cell lines (ACP-03, SKMEL-19 and HCT-116) by using MTT assay. Schiff bases 4b and 4o exhibited promising cytotoxicity against ACP-03 and SKMEL-19, respectively, with IC₅₀ values lower than 5 μM. This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against cancer. Full article

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

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17 pages, 1935 KiB

Open AccessReview

Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls

by Hezekiel Mathambo Kumalo, Soumendranath Bhakat and Mahmoud E. S. Soliman^*

Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4000, South Africa

Molecules 2015, 20(2), 1984-2000; https://doi.org/10.3390/molecules20021984 - 27 Jan 2015

Cited by 124 | Viewed by 18300

Abstract

he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds [...] Read more.

he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds to completion rather than to equilibrium. Covalent inhibitors possessed some significant advantages over non-covalent inhibitors such as covalent warheads can target rare, non-conserved residue of a particular target protein and thus led to development of highly selective inhibitors, covalent inhibitors can be effective in targeting proteins with shallow binding cleavage which will led to development of novel inhibitors with increased potency than non-covalent inhibitors. Several computational approaches have been developed to simulate covalent interactions; however, this is still a challenging area to explore. Covalent molecular docking has been recently implemented in the computer-aided drug design workflows to describe covalent interactions between inhibitors and biological targets. In this review we highlight: (i) covalent interactions in biomolecular systems; (ii) the mathematical framework of covalent molecular docking; (iii) implementation of covalent docking protocol in drug design workflows; (iv) applications covalent docking: case studies and (v) shortcomings and future perspectives of covalent docking. To the best of our knowledge; this review is the first account that highlights different aspects of covalent docking with its merits and pitfalls. We believe that the method and applications highlighted in this study will help future efforts towards the design of irreversible inhibitors. Full article

(This article belongs to the Special Issue Molecular Docking in Drug Design)

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13 pages, 1049 KiB

Open AccessArticle

Development and Validation of 697 Novel Polymorphic Genomic and EST-SSR Markers in the American Cranberry (Vaccinium macrocarpon Ait.)

by Brandon Schlautman^1,*, Diego Fajardo², Tierney Bougie¹, Eric Wiesman³, James Polashock⁴, Nicholi Vorsa⁵, Shawn Steffan³ and Juan Zalapa^1,3,*

¹ Department of Horticulture, University of Wisconsin-Madison, 1575 Linden Dr. Madison, WI 53706, USA

² National Center for Genome Resources, 2935 Rodeo Park Dr. East, Sante Fe, NM 87505, USA

³ USDA-ARS, Vegetable Crops Research Unit, University of Wisconsin, Madison, WI 53706, USA

⁴ USDA-ARS, Genetic Improvement of Fruits and Vegetables Laboratory, Rutgers University Chatsworth, NJ 08019, USA

⁵ Blueberry and Cranberry Research and Extension Center, Rutgers University, Chatsworth, NJ 08019, USA

Molecules 2015, 20(2), 2001-2013; https://doi.org/10.3390/molecules20022001 - 27 Jan 2015

Cited by 37 | Viewed by 8408

Abstract

The American cranberry, Vaccinium macrocarpon Ait., is an economically important North American fruit crop that is consumed because of its unique flavor and potential health benefits. However, a lack of abundant, genome-wide molecular markers has limited the adoption of modern molecular assisted selection [...] Read more.

The American cranberry, Vaccinium macrocarpon Ait., is an economically important North American fruit crop that is consumed because of its unique flavor and potential health benefits. However, a lack of abundant, genome-wide molecular markers has limited the adoption of modern molecular assisted selection approaches in cranberry breeding programs. To increase the number of available markers in the species, this study identified, tested, and validated microsatellite markers from existing nuclear and transcriptome sequencing data. In total, new primers were designed, synthesized, and tested for 979 SSR loci; 697 of the markers amplified allele patterns consistent with single locus segregation in a diploid organism and were considered polymorphic. Of the 697 polymorphic loci, 507 were selected for additional genetic diversity and segregation analyses in 29 cranberry genotypes. More than 95% of the 507 loci did not display segregation distortion at the p < 0.05 level, and contained moderate to high levels of polymorphism with a polymorphic information content >0.25. This comprehensive collection of developed and validated microsatellite loci represents a substantial addition to the molecular tools available for geneticists, genomicists, and breeders in cranberry and Vaccinium. Full article

(This article belongs to the Section Molecular Diversity)

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20 pages, 876 KiB

Open AccessReview

Insecticidal Activity of Plant Lectins and Potential Application in Crop Protection

by Maria Lígia R. Macedo^1,*, Caio F. R. Oliveira^1,2 and Carolina T. Oliveira¹

¹ Department of Food Technology and Public Health, University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul 79070-900, Brazil

² Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Sao Paulo 13083-862, Brazil

Molecules 2015, 20(2), 2014-2033; https://doi.org/10.3390/molecules20022014 - 27 Jan 2015

Cited by 120 | Viewed by 17107

Abstract

Lectins constitute a complex group of proteins found in different organisms. These proteins constitute an important field for research, as their structural diversity and affinity for several carbohydrates makes them suitable for numerous biological applications. This review addresses the classification and insecticidal activities [...] Read more.

Lectins constitute a complex group of proteins found in different organisms. These proteins constitute an important field for research, as their structural diversity and affinity for several carbohydrates makes them suitable for numerous biological applications. This review addresses the classification and insecticidal activities of plant lectins, providing an overview of the applicability of these proteins in crop protection. The likely target sites in insect tissues, the mode of action of these proteins, as well as the use of lectins as biotechnological tools for pest control are also described. The use of initial bioassays employing artificial diets has led to the most recent advances in this field, such as plant breeding and the construction of fusion proteins, using lectins for targeting the delivery of toxins and to potentiate expected insecticide effects. Based on the data presented, we emphasize the contribution that plant lectins may make as tools for the development of integrated insect pest control strategies. Full article

(This article belongs to the Special Issue Lectins)

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27 pages, 934 KiB

Open AccessArticle

The Synthesis and Antitumor Activity of Twelve Galloyl Glucosides

by Chang-Wei Li, Hua-Jin Dong and Cheng-Bin Cui^*

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Molecules 2015, 20(2), 2034-2060; https://doi.org/10.3390/molecules20022034 - 27 Jan 2015

Cited by 34 | Viewed by 10737

Abstract

Twelve galloyl glucosides 1–12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9), [...] Read more.

Twelve galloyl glucosides 1–12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9), ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11) and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12), are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1), 1,4,6-tri-O-galloyl-β-D-glucopyranose (2), 1,2-di-O-galloyl-β-D-glucopyranose (3), 1,3-di-O-galloyl-β-D-glucopyranose (4), 1,2,3-tri-O-galloyl-α-D-glucopyranose (6) and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10), were synthesized for the first time in the present study. In in vitro MTT assay, 1–12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC₅₀ values were determined to be varied in 17.2–124.7 μM on the tested three human cancer cell lines. In addition, compounds 1–12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control. Full article

(This article belongs to the Section Organic Chemistry)

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20 pages, 794 KiB

Open AccessArticle

Distinctive Anthocyanin Accumulation Responses to Temperature and Natural UV Radiation of Two Field-Grown Vitis vinifera L. Cultivars

by Ana Fernandes de Oliveira^1,*, Luca Mercenaro¹, Alessandra Del Caro¹, Luca Pretti² and Giovanni Nieddu¹

¹ Department of Agriculture, University of Sassari, Viale Italia 39, Sassari 07100, Italy

² Porto Conte Ricerche Srl, S.P. 55 Porto Conte/Capo Caccia, Tramariglio-Alghero (SS) 07041, Italy

Molecules 2015, 20(2), 2061-2080; https://doi.org/10.3390/molecules20022061 - 27 Jan 2015

Cited by 57 | Viewed by 7640

Abstract

The responses of two red grape varieties, Bovale Grande (syn. Carignan) and Cannonau (syn. Grenache), to temperature and natural UV radiation were studied in a three-years field experiment conducted in Sardinia (Italy), under Mediterranean climate conditions. Vines were covered with plastic films with [...] Read more.

The responses of two red grape varieties, Bovale Grande (syn. Carignan) and Cannonau (syn. Grenache), to temperature and natural UV radiation were studied in a three-years field experiment conducted in Sardinia (Italy), under Mediterranean climate conditions. Vines were covered with plastic films with different transmittances to UV radiation and compared to uncovered controls. Light intensity and spectral composition at the fruit zone were monitored and berry skin temperature was recorded from veraison. Total skin anthocyanin content (TSA) and composition indicated positive but inconsistent effects of natural UV light. Elevated temperatures induced alterations to a greater extent, decreasing TSA and increasing the degree of derivatives acylation. In Cannonau total soluble solids increases were not followed by increasing TSA as in Bovale Grande, due to both lower phenolic potential and higher sensitivity to permanence of high temperatures. Multi linear regression analysis tested the effects of different ranges of temperature as source of variation on anthocyanin accumulation patterns. To estimate the thermal time for anthocyanin accumulation, the use of normal heat hours model had benefit from the addition of predictor variables that take into account the permanence of high (>35 °C) and low (<15 °C and <17 °C) temperatures during ripening. Full article

(This article belongs to the Special Issue Anthocyanins)

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19 pages, 4619 KiB

Open AccessArticle

Evaluation of the Radiolabeled Boronic Acid-Based FAP Inhibitor MIP-1232 for Atherosclerotic Plaque Imaging

by Romana Meletta¹, Adrienne Müller Herde¹, Aristeidis Chiotellis¹, Malsor Isa¹, Zoran Rancic², Nicole Borel³, Simon M. Ametamey¹, Stefanie D. Krämer^1,* and Roger Schibli^1,4

¹ Department of Chemistry and Applied Bioscience of ETH Zurich, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland

² Division of Cardiovascular Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland

³ Institute for Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, 8057 Zurich, Switzerland

⁴ Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland

Molecules 2015, 20(2), 2081-2099; https://doi.org/10.3390/molecules20022081 - 27 Jan 2015

Cited by 44 | Viewed by 10052

Abstract

Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of [...] Read more.

Research towards the non-invasive imaging of atherosclerotic plaques is of high clinical priority as early recognition of vulnerable plaques may reduce the incidence of cardiovascular events. The fibroblast activation protein alpha (FAP) was recently proposed as inflammation-induced protease involved in the process of plaque vulnerability. In this study, FAP mRNA and protein levels were investigated by quantitative polymerase chain reaction and immunohistochemistry, respectively, in human endarterectomized carotid plaques. A published boronic-acid based FAP inhibitor, MIP-1232, was synthetized and radiolabeled with iodine-125. The potential of this radiotracer to image plaques was evaluated by in vitro autoradiography with human carotid plaques. Specificity was assessed with a xenograft with high and one with low FAP level, grown in mice. Target expression analyses revealed a moderately higher protein level in atherosclerotic plaques than normal arteries correlating with plaque vulnerability. No difference in expression was determined on mRNA level. The radiotracer was successfully produced and accumulated strongly in the FAP-positive SK-Mel-187 melanoma xenograft in vitro while accumulation was negligible in an NCI-H69 xenograft with low FAP levels. Binding of the tracer to endarterectomized tissue was similar in plaques and normal arteries, hampering its use for atherosclerosis imaging. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 809 KiB

Open AccessArticle

Metabolic Profiling of the Uncaria Hook Alkaloid Geissoschizine Methyl Ether in Rat and Human Liver Microsomes Using High-Performance Liquid Chromatography with Tandem Mass Spectrometry

by Hirotaka Kushida^1,*, Takashi Matsumoto¹

, Yasushi Igarashi², Hiroaki Nishimura², Junko Watanabe¹, Kazuya Maemura¹ and Yoshio Kase¹

¹ Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan

² Kampo Formulation Development Center, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan

Molecules 2015, 20(2), 2100-2114; https://doi.org/10.3390/molecules20022100 - 27 Jan 2015

Cited by 12 | Viewed by 8062

Abstract

Geissoschizine methyl ether (GM) is an indole alkaloid found in Uncaria hook, which is a galenical constituent of yokukansan, a traditional Japanese medicine. GM has been identified as the active component responsible for anti-aggressive effects. In this study, the metabolic profiling of [...] Read more.

Geissoschizine methyl ether (GM) is an indole alkaloid found in Uncaria hook, which is a galenical constituent of yokukansan, a traditional Japanese medicine. GM has been identified as the active component responsible for anti-aggressive effects. In this study, the metabolic profiling of GM in rat and human liver microsomes was investigated. Thirteen metabolites of GM were elucidated and identified using a high-performance liquid chromatography with tandem mass spectrometry method, and their molecular structures were proposed on the basis of the characteristics of their precursor ions, product ions, and chromatographic retention times. There were no differences in the metabolites between the rat and human liver microsomes. Among the 13 identified metabolites, there were two demethylation metabolites, one dehydrogenation metabolite, three methylation metabolites, three oxidation metabolites, two water-adduct metabolites, one di-demethylation metabolite, and one water-adduct metabolite followed by oxidation. The metabolic pathways of GM were proposed on the basis of this study. This study will be helpful in understanding the metabolic routes of GM and related Uncaria hook alkaloids, and provide useful information on the pharmacokinetics and pharmacodynamics. This is the first report that describes the separation and identification of GM metabolites in rat and human liver microsomes. Full article

(This article belongs to the Section Metabolites)

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23 pages, 1757 KiB

Open AccessArticle

Synthesis, Crystal Structure, Spectroscopic Properties and Potential Biological Activities of Salicylate‒Neocuproine Ternary Copper(II) Complexes

by Lenka Kucková^1,*, Klaudia Jomová², Andrea Švorcová², Marián Valko¹, Peter Segľa³, Ján Moncoľ³

and Jozef Kožíšek¹

¹ Department of Physical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, Bratislava SK-812 37, Slovak Republic

² Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University, Trieda A. Hlinku 1, Nitra SK-949 74, Slovak Republic

³ Department of Inorganic Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinského 9, Bratislava SK-812 37, Slovak Republic

Molecules 2015, 20(2), 2115-2137; https://doi.org/10.3390/molecules20022115 - 27 Jan 2015

Cited by 83 | Viewed by 11874

Abstract

Mixed ligand copper(II) complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II) complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo) and salicylate ligands [...] Read more.

Mixed ligand copper(II) complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II) complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo) and salicylate ligands (Sal) are reported. In addition, the crystal structures of ([Cu(H₂O)(5-Cl-Sal)(Neo)] (1), [Cu(μ-Sal)(Neo)]₂ (2), Cu₂(μ-5-Cl-Sal)(5-Cl-HSal)₂(Neo)₂]·EtOH (3)) were determined. In order to compare structural and biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction show that prepared complexes form three types of crystal structures in a given system: monomeric, dimeric and dinuclear complex. The preliminary study on the DNA cleavage activity has shown that the complexes under study behave as the chemical nucleases in the presence of added hydrogen peroxide with slight differences in the activity (1 > 2 > 3). The complexes 1 and 2 exhibited nuclease activity itself indicating the interaction of complexes with the DNA. It has been proposed that the enhanced destructive effect of the complexes 1 and 2 on the DNA is a result of two possible mechanisms of action: (i) the conversion of closed circular DNA (form I) to the nicked DNA (form II) caused by the copper complex itself and (ii) damage of DNA by Reactive Oxygen Species (ROS)—products of the interaction of copper with hydrogen peroxide by means of Fenton reaction (hydroxyl radicals). Thus the biological activity of the prepared Cu(II) complexes containing derivatives of salicylic acid and phenanthroline molecules is substantiated by two independent mechanisms. While derivatives of salicylic acids in the coordination sphere of copper complexes are responsible for radical-scavenging activity (predominantly towards superoxide radical anion), the presence of chelating ligand 2,9-dimethyl-1,10-phenanthroline significantly enhances capability of Cu(II) complexes binding to DNA via intercalation. Full article

(This article belongs to the Section Medicinal Chemistry)

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27 pages, 1539 KiB

Open AccessReview

Tyrosine Sulfation as a Protein Post-Translational Modification

by Yuh-Shyong Yang^1,*, Chen-Chu Wang^1,†, Bo-Han Chen^1,†, You-Hua Hou¹, Kuo-Sheng Hung^2,* and Yi-Chih Mao¹

¹ Department of Biological Science and Technology, National Chiao Tung University, 75 Po-Ai Street, Hsinchu 30068, Taiwan

² Department of Neurosurgery, Center of Excellence for Clinical Trial and Research, Taipei Medical University-Wan Fang Medical Center, Taipei 11696, Taiwan

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2138-2164; https://doi.org/10.3390/molecules20022138 - 28 Jan 2015

Cited by 112 | Viewed by 18341

Abstract

Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, [...] Read more.

Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, the significance of PTS under physiological conditions and its link to diseases have just begun to be appreciated in recent years. PTS is catalyzed by tyrosylprotein sulfotransferase (TPST) through transfer of an activated sulfate from 3'-phosphoadenosine-5'-phosphosulfate to tyrosine in a variety of proteins and peptides. Currently, only a small fraction of sulfated proteins is known and the understanding of the biological sulfation mechanisms is still in progress. In this review, we give an introductory and selective brief review of PTS and then summarize the basic biochemical information including the activity and the preparation of TPST, methods for the determination of PTS, and kinetics and reaction mechanism of TPST. This information is fundamental for the further exploration of the function of PTS that induces protein-protein interactions and the subsequent biochemical and physiological reactions. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment)

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11 pages, 788 KiB

Open AccessArticle

New Lignans and Iridoid Glycosides from Dipsacus asper Wall

by Xinguang Sun¹, Guoxu Ma¹, Dawei Zhang¹, Wenhua Huang¹, Gang Ding^1,*, Huagang Hu², Guangzhong Tu³ and Baolin Guo^1,*

¹ Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

² State Nationalities Affairs Commission and Department of Educational Key Lab of Minority Traditional Medicine, MINZU University of China, Beijing 10081, China

³ Beijing Institute of Microchemistry, Beijing 100091, China

Molecules 2015, 20(2), 2165-2175; https://doi.org/10.3390/molecules20022165 - 28 Jan 2015

Cited by 27 | Viewed by 7384

Abstract

Six new compounds, including four new lignans, dipsalignan A (1), B–D (3–5), and two new bis-iridoid glycoside dimmers, dipsanosides M (7) and N (8), together with two known compounds (2) and [...] Read more.

Six new compounds, including four new lignans, dipsalignan A (1), B–D (3–5), and two new bis-iridoid glycoside dimmers, dipsanosides M (7) and N (8), together with two known compounds (2) and (6), have been isolated from the roots of Dipsacus asper Wall. Their structures were established on the basis of spectroscopic data (MS, 1D, 2D NMR, and CD) and chemical methods. All the isolated compounds were tested against human immunodeficiency virus-1 (HIV-1) integrase inhibition activities, and only compounds 1, 2, 7, and 8 displayed weak activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1351 KiB

Open AccessArticle

The Content of Phenolic Compounds in Leaf Tissues of Aesculus glabra and Aesculus parviflora Walt.

by Jan Oszmiański¹, Joanna Kolniak-Ostek^1,* and Agata Biernat²

¹ Department of Fruit, Vegetable and Grain Technology, Wroclaw University of Environmental and Life Sciences, 37/41 Chełmońskiego St., Wroclaw 51-630, Poland

² Department of Biology and Pharmaceutical Botany with Garden of Medicinal Plants, University of Medicine in Wrocław, Kochanowskiego 12, Wrocław 51-601, Poland

Molecules 2015, 20(2), 2176-2189; https://doi.org/10.3390/molecules20022176 - 28 Jan 2015

Cited by 36 | Viewed by 7840

Abstract

In plants, flavonoids play an important role in biological processes. They are involved in UV-scavenging, fertility and disease resistance. Therefore, in this study, we attempted to quantify and characterize phenolic compounds in Aesculus parviflora Walt. leaves and Aesculus glabra leaves partly suffering from [...] Read more.

In plants, flavonoids play an important role in biological processes. They are involved in UV-scavenging, fertility and disease resistance. Therefore, in this study, we attempted to quantify and characterize phenolic compounds in Aesculus parviflora Walt. leaves and Aesculus glabra leaves partly suffering from attack by a leaf mining insect (C. ohridella). A total of 28 phenolic compounds belonging to the hydroxycinnamic acid, flavan-3-ols and flavonol groups were identified and quantified in Aesculus parviflora and A. glabra leaf extracts. Significantly decreased concentrations of some phenolic compounds, especially of flavan-3-ols, were observed in infected leaves compared to the non-infected ones. Additionally, a higher content of polymeric procyanidins in leaves of Aesculus parviflora than in Aesculus glabra may explain their greater resistance to C. ohridella insects. Full article

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

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18 pages, 724 KiB

Open AccessArticle

Characterisation of Mediterranean Grape Pomace Seed and Skin Extracts: Polyphenolic Content and Antioxidant Activity

by Isabelle Ky^1,2 and Pierre-Louis Teissedre^1,2,*

¹ Univ Bordeaux, ISVV, EA 4577 Œnologie, 210 Chemin de Leysotte, Villenave d'Ornon F-33140, France

² INRA, ISVV, USC 1366 Œnologie, 210 Chemin de Leysotte, Villenave d'Ornon F-33140, France

Molecules 2015, 20(2), 2190-2207; https://doi.org/10.3390/molecules20022190 - 29 Jan 2015

Cited by 105 | Viewed by 11829

Abstract

Grape pomace seeds and skins from different Mediterranean varieties (Grenache [GRE], Syrah [SYR], Carignan [CAR], Mourvèdre [MOU] and Alicante [ALI]) were extracted using water and water/ethanol 70% in order to develop edible extracts (an aqueous extract [EAQ] and a 70% hydro-alcoholic extract [EA70]) [...] Read more.

Grape pomace seeds and skins from different Mediterranean varieties (Grenache [GRE], Syrah [SYR], Carignan [CAR], Mourvèdre [MOU] and Alicante [ALI]) were extracted using water and water/ethanol 70% in order to develop edible extracts (an aqueous extract [EAQ] and a 70% hydro-alcoholic extract [EA70]) for potential use in nutraceutical or cosmetic formulations. In this study, global content (total polyphenols, total anthocyanins and total tannins), flavan-3-ols and anthocyanins were assessed using HPLC-UV-Fluo-MSⁿ. In addition, extract potential was evaluated by four different assays: Oxygen Radical Absorbance Capacity (ORAC), Ferric Reducing Antioxidant Potential assay (FRAP), Trolox equivalent antioxidant capacity (TEAC) or ABTS assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. As expected, seed pomace extracts contained higher amounts of polyphenols then skin pomace extracts. Indeed, seeds from Syrah contained a particularly important amount of total polyphenols and tannins in both type of extract (up to 215.84 ± 1.47 mg of gallic acid equivalent [GAE]/g dry weight (DW) and 455.42 ± 1.84 mg/g DW, respectively). These extracts also expressed the highest antioxidant potential with every test. For skins, the maximum total phenolic was found in Alicante EAQ (196.71 ± 0.37 mg GAE/g DW) and in Syrah EA70 (224.92 ± 0.18 mg GAE/g DW). Results obtained in this article constitute a useful tool for the pre-selection of grape pomace seed and skin extracts for nutraceutical purposes. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

21 pages, 2025 KiB

Open AccessReview

The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation

by Xaver Koenig^* and Karlheinz Hilber^*

Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, Vienna 1090, Austria

Molecules 2015, 20(2), 2208-2228; https://doi.org/10.3390/molecules20022208 - 29 Jan 2015

Cited by 91 | Viewed by 29107

Abstract

The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is [...] Read more.

The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine in dozens of clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of ibogaine, have been accumulating. These adverse reactions were hypothesised to be associated with ibogaine’s propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine’s effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti- addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener with anti-addictive properties, are also considered. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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43 pages, 2601 KiB

Open AccessReview

Human Lectins and Their Roles in Viral Infections

by Christopher P. Mason and Alexander W. Tarr^*

School of Life Sciences and Biomedical Research Unit in Gastroenterology, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2UH, UK

Molecules 2015, 20(2), 2229-2271; https://doi.org/10.3390/molecules20022229 - 29 Jan 2015

Cited by 97 | Viewed by 19486

Abstract

Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs) that recognise viral pathogen-associated molecular patterns (PAMPs) including viral glycoproteins. In this [...] Read more.

Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs) that recognise viral pathogen-associated molecular patterns (PAMPs) including viral glycoproteins. In this review we discuss the contribution of soluble and membrane-associated PRRs to immunity against virus pathogens, and the potential role of these molecules in facilitating virus replication. These processes are illustrated with examples of viruses including human immunodeficiency virus (HIV), hepatitis C virus (HCV) and Ebola virus (EBOV). We focus on the structure, function and genetics of the well-characterised C-type lectin mannose-binding lectin, the ficolins, and the membrane-bound CD209 proteins expressed on dendritic cells. The potential for lectin-based antiviral therapies is also discussed. Full article

(This article belongs to the Special Issue Lectins)

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24 pages, 3659 KiB

Open AccessReview

The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis

by Yang Liu^1,2,3, Jianying Liu¹, Xiaojing Pang¹, Tao Liu⁴, Zhijie Ning⁵ and Gong Cheng^1,2,6,*

¹ Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China

² Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China

³ School of Life Science, Tsinghua University, Beijing 100084, China

⁴ Center for Reproductive Medicine, Tai'an Central Hospital, Tai'an 271000, China

⁵ Ji'nan Infectious Diseases Hospital, Ji'nan 250021, China

⁶ Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China

Molecules 2015, 20(2), 2272-2295; https://doi.org/10.3390/molecules20022272 - 29 Jan 2015

Cited by 51 | Viewed by 12602

Abstract

Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) [...] Read more.

Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) modules. Many studies have indicated that the direct recognition of particular oligosaccharides on viral components by lectins is important for interactions between hosts and viruses. Herein, we aim to globally review the roles of this recognition by animal lectins in antiviral immune responses and viral pathogenesis. The different classes of mammalian lectins can either recognize carbohydrates to activate host immunity for viral elimination or can exploit those carbohydrates as susceptibility factors to facilitate viral entry, replication or assembly. Additionally, some arthropod C-type lectins were recently identified as key susceptibility factors that directly interact with multiple viruses and then facilitate infection. Summarization of the pleiotropic roles of direct viral recognition by animal lectins will benefit our understanding of host-virus interactions and could provide insight into the role of lectins in antiviral drug and vaccine development. Full article

(This article belongs to the Special Issue Lectins)

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14 pages, 758 KiB

Open AccessArticle

A Facile Ionic Liquid Promoted Synthesis, Cholinesterase Inhibitory Activity and Molecular Modeling Study of Novel Highly Functionalized Spiropyrrolidines

by Abdulrahman I. Almansour¹, Raju Suresh Kumar^1,*, Natarajan Arumugam¹, Alireza Basiri², Yalda Kia³, Mohamed Ashraf Ali⁴, Mehvish Farooq⁵ and Vikneswaran Murugaiyah²

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

² School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Malaysia

³ School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Malaysia

⁴ Pharmacogenetic and Novel Therapeutic Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Malaysia

⁵ Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK

Molecules 2015, 20(2), 2296-2309; https://doi.org/10.3390/molecules20022296 - 29 Jan 2015

Cited by 43 | Viewed by 6574

Abstract

A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC₅₀ value of 1.57 µM against acethylcholinesterase (AChE). [...] Read more.

A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC₅₀ value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 909 KiB

Open AccessArticle

Soy Isoflavones in Nutritionally Relevant Amounts Have Varied Nutrigenomic Effects on Adipose Tissue

by Elena Giordano¹, Alberto Dávalos¹, Maria Carmen Crespo¹, Joao Tomé-Carneiro¹

, Diego Gómez-Coronado^2,3 and Francesco Visioli^1,4,*

¹ Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)—Food, CEI UAM+CSIC, Carretera de Cantoblanco 8, Madrid 28049, Spain

² Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid 28034, Spain

³ CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid 28029, Spain

⁴ Department of Molecular Medicine, University of Padova, Padova 35121, Italy

Molecules 2015, 20(2), 2310-2322; https://doi.org/10.3390/molecules20022310 - 30 Jan 2015

Cited by 16 | Viewed by 8365

Abstract

Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that [...] Read more.

Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that soy foods and supplements positively impact human health has become increasingly controversial among the general public because of the reported estrogenic activities of soy isoflavones. In this study, we investigated the nutrigenomic actions of soy isoflavones (in nutritionally-relevant amounts) with a specific focus on the adipose tissue, due to its pivotal role in cardiometabolism. Young C57BL/6 mice were maintained for eight weeks under two different diet regimes: (1) purified control diet; or (2) purified control diet supplemented with 0.45 g% soybean dry purified extract (a genistein/daidzein mix). Soy isoflavones increased plasma total cholesterol concentrations and decreased triglyceride ones. Circulating leptin levels was also increased by soy consumption. Differentially expressed genes in adipose tissue were classified according to their role(s) in cellular or metabolic pathways. Our data show that soy isoflavones, administered in nutritionally-relevant amounts, have diverse nutrigenomic effects on adipose tissue. Taking into account the moderate average exposure to such molecules, their impact on cardiovascular health needs to be further investigated to resolve the issue of whether soy consumption does indeed increase or decrease cardiovascular risk. Full article

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

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26 pages, 2689 KiB

Open AccessReview

Targeting Carbonic Anhydrase IX Activity and Expression

by Brian P. Mahon^†, Melissa A. Pinard^† and Robert McKenna^*

¹ Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2323-2348; https://doi.org/10.3390/molecules20022323 - 30 Jan 2015

Cited by 114 | Viewed by 15120

Abstract

Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance [...] Read more.

Metastatic tumors are often hypoxic exhibiting a decrease in extracellular pH (~6.5) due to a metabolic transition described by the Warburg Effect. This shift in tumor cell metabolism alters the tumor milieu inducing tumor cell proliferation, angiogenesis, cell motility, invasiveness, and often resistance to common anti-cancer treatments; hence hindering treatment of aggressive cancers. As a result, tumors exhibiting this phenotype are directly associated with poor prognosis and decreased survival rates in cancer patients. A key component to this tumor microenvironment is carbonic anhydrase IX (CA IX). Knockdown of CA IX expression or inhibition of its activity has been shown to reduce primary tumor growth, tumor proliferation, and also decrease tumor resistance to conventional anti-cancer therapies. As such several approaches have been taken to target CA IX in tumors via small-molecule, anti-body, and RNAi delivery systems. Here we will review recent developments that have exploited these approaches and provide our thoughts for future directions of CA IX targeting for the treatment of cancer. Full article

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

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15 pages, 2655 KiB

Open AccessArticle

Preparation of a Titania/X-Zeolite/Porous Glass Composite Photocatalyst Using Hydrothermal and Drop Coating Processes

by Atsuo Yasumori^1,2,*, Sayaka Yanagida^1,2 and Jun Sawada¹

¹ Department of Materials Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan

² Photocatalysis International Research Center, Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan

Molecules 2015, 20(2), 2349-2363; https://doi.org/10.3390/molecules20022349 - 30 Jan 2015

Cited by 14 | Viewed by 7839

Abstract

Combinations of TiO₂ photocatalysts and various adsorbents have been widely studied for the adsorption and photocatalytic decomposition of gaseous pollutants such as volatile organic compounds (VOCs). Herein, a TiO₂-zeolite-porous glass composite was prepared using melt-quenching and partial sintering, hydrothermal treatment, [...] Read more.

Combinations of TiO₂ photocatalysts and various adsorbents have been widely studied for the adsorption and photocatalytic decomposition of gaseous pollutants such as volatile organic compounds (VOCs). Herein, a TiO₂-zeolite-porous glass composite was prepared using melt-quenching and partial sintering, hydrothermal treatment, and drop coating for preparation of the porous glass support and X-zeolite and their combination with TiO₂, respectively. The obtained composite comprised anatase phase TiO₂, X-zeolite, and the porous glass support, which were combined at the micro to nanometer scales. The composite had a relatively high specific surface area of approximately 25 m²/g and exhibited a good adsorption capacity for 2-propanol. These data indicated that utilization of this particular phase-separated glass as the support was appropriate for the formation of the bulk photocatalyst-adsorbent composite. Importantly, the photocatalytic decomposition of adsorbed 2-propanol proceeded under UV light irradiation. The 2-propanol was oxidized to acetone and then trapped by the X-zeolite rather than being released to the atmosphere. Consequently, it was demonstrated that the micrometer-scaled combination of TiO₂ and zeolite in the bulk form is very useful for achieving both the removal of gaseous organic pollutants and decreasing the emission of harmful intermediates. Full article

(This article belongs to the Special Issue Photocatalysis)

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24 pages, 2152 KiB

Open AccessReview

Elderberries: A Source of Ribosome-Inactivating Proteins with Lectin Activity

by Jesús Tejero^1,†, Pilar Jiménez^1,†, Emiliano J. Quinto¹, Damián Cordoba-Diaz²

, Manuel Garrosa³, Manuel Cordoba-Diaz²

, Manuel J. Gayoso³ and Tomás Girbés^1,*

¹ Nutrición y Bromatología, Facultad de Medicina and Centro de Investigación en Nutrición, Alimentación y Dietética (CINAD), Universidad de Valladolid, Valladolid 47005, Spain

² Farmacia y Tecnología Farmacéutica, Facultad de Farmacia and Instituto Universitario de Farmacia Industrial (IUFI), Universidad Complutense de Madrid, Madrid 28040, Spain

³ Biología Celular, Histología y Farmacología, Facultad de Medicina and Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Valladolid, Valladolid 47005, Spain

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2364-2387; https://doi.org/10.3390/molecules20022364 - 30 Jan 2015

Cited by 30 | Viewed by 11008

Abstract

Sambucus (Adoxaceae) species have been used for both food and medicine purposes. Among these, Sambucus nigra L. (black elder), Sambucus ebulus L. (dwarf elder), and Sambucus sieboldiana L. are the most relevant species studied. Their use has been somewhat restricted due [...] Read more.

Sambucus (Adoxaceae) species have been used for both food and medicine purposes. Among these, Sambucus nigra L. (black elder), Sambucus ebulus L. (dwarf elder), and Sambucus sieboldiana L. are the most relevant species studied. Their use has been somewhat restricted due to the presence of bioactive proteins or/and low molecular weight compounds whose ingestion could trigger deleterious effects. Over the last few years, the chemical and pharmacological characteristics of Sambucus species have been investigated. Among the proteins present in Sambucus species both type 1, and type 2 ribosome-inactivating proteins (RIPs), and hololectins have been reported. The biological role played by these proteins remains unknown, although they are conjectured to be involved in defending plants against insect predators and viruses. These proteins might have an important impact on the nutritional characteristics and food safety of elderberries. Type 2 RIPs are able to interact with gut cells of insects and mammals triggering a number of specific and mostly unknown cell signals in the gut mucosa that could significantly affect animal physiology. In this paper, we describe all known RIPs that have been isolated to date from Sambucus species, and comment on their antiviral and entomotoxic effects, as well as their potential uses. Full article

(This article belongs to the Special Issue Lectins)

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17 pages, 871 KiB

Open AccessArticle

A Sorghum MYB Transcription Factor Induces 3-Deoxyanthocyanidins and Enhances Resistance against Leaf Blights in Maize

by Farag Ibraheem^1,2,3,†, Iffa Gaffoor^1,†, Qixian Tan¹, Chi-Ren Shyu⁴

and Surinder Chopra^1,2,*

¹ Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA

² Intercollege Graduate Degree Program in Plant Biology, Pennsylvania State University, University Park, PA 16802, USA

³ Botany Department, Faculty of Science, Mansoura University, AlMansoura, 35516, Egypt

⁴ MU Informatics Institute, University of Missouri, Columbia, MO 65201, USA

^† These authors contributed equally to the work.

Molecules 2015, 20(2), 2388-2404; https://doi.org/10.3390/molecules20022388 - 30 Jan 2015

Cited by 65 | Viewed by 10140

Abstract

Sorghum responds to the ingress of the fungal pathogen Colletotrichum sublineolum through the biosynthesis of 3-deoxyanthocyanidin phytoalexins at the site of primary infection. Biosynthesis of 3-deoxyanthocyanidins in sorghum requires a MYB transcription factor encoded by yellow seed1 (y1), an orthologue of [...] Read more.

Sorghum responds to the ingress of the fungal pathogen Colletotrichum sublineolum through the biosynthesis of 3-deoxyanthocyanidin phytoalexins at the site of primary infection. Biosynthesis of 3-deoxyanthocyanidins in sorghum requires a MYB transcription factor encoded by yellow seed1 (y1), an orthologue of the maize gene pericarp color1 (p1). Maize lines with a functional p1 and flavonoid structural genes do not produce foliar 3-deoxyanthocyanidins in response to fungal ingress. To perform a comparative metabolic analysis of sorghum and maize 3-deoxyanthocyanidin biosynthetic pathways, we developed transgenic maize lines expressing the sorghum y1 gene. In maize, the y1 transgene phenocopied p1-regulated pigment accumulation in the pericarp and cob glumes. LC-MS profiling of fungus-challenged Y1-maize leaves showed induction of 3-deoxyanthocyanidins, specifically luteolinidin. Y1-maize plants also induced constitutive and higher levels of flavonoids in leaves. In response to Colletotrichum graminicola, Y1-maize showed a resistance response. Full article

(This article belongs to the Special Issue Phytoalexins: Current Progress and Future Prospects)

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20 pages, 1360 KiB

Open AccessReview

Isotope Effects on Chemical Shifts in the Study of Intramolecular Hydrogen Bonds

by Poul Erik Hansen

Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, Roskilde DK-4000, Denmark

Molecules 2015, 20(2), 2405-2424; https://doi.org/10.3390/molecules20022405 - 30 Jan 2015

Cited by 30 | Viewed by 7980

Abstract

The paper deals with the use of isotope effects on chemical shifts in characterizing intramolecular hydrogen bonds. Both so-called resonance-assisted (RAHB) and non-RAHB systems are treated. The importance of RAHB will be discussed. Another very important issue is the borderline between “static” and [...] Read more.

The paper deals with the use of isotope effects on chemical shifts in characterizing intramolecular hydrogen bonds. Both so-called resonance-assisted (RAHB) and non-RAHB systems are treated. The importance of RAHB will be discussed. Another very important issue is the borderline between “static” and tautomeric systems. Isotope effects on chemical shifts are particularly useful in such studies. All kinds of intramolecular hydrogen bonded systems will be treated, typical hydrogen bond donors: OH, NH, SH and NH⁺, typical acceptors C=O, C=N, C=S C=N⁻. The paper will be deal with both secondary and primary isotope effects on chemical shifts. These two types of isotope effects monitor the same hydrogen bond, but from different angles. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding)

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20 pages, 875 KiB

Open AccessReview

A Review of Odd-Chain Fatty Acid Metabolism and the Role of Pentadecanoic Acid (C15:0) and Heptadecanoic Acid (C17:0) in Health and Disease

by Benjamin Jenkins, James A. West and Albert Koulman^*

MRC HNR, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK

Molecules 2015, 20(2), 2425-2444; https://doi.org/10.3390/molecules20022425 - 30 Jan 2015

Cited by 374 | Viewed by 35047

Abstract

The role of C17:0 and C15:0 in human health has recently been reinforced following a number of important biological and nutritional observations. Historically, odd chain saturated fatty acids (OCS-FAs) were used as internal standards in GC-MS methods of total fatty acids and LC-MS [...] Read more.

The role of C17:0 and C15:0 in human health has recently been reinforced following a number of important biological and nutritional observations. Historically, odd chain saturated fatty acids (OCS-FAs) were used as internal standards in GC-MS methods of total fatty acids and LC-MS methods of intact lipids, as it was thought their concentrations were insignificant in humans. However, it has been thought that increased consumption of dairy products has an association with an increase in blood plasma OCS-FAs. However, there is currently no direct evidence but rather a casual association through epidemiology studies. Furthermore, a number of studies on cardiometabolic diseases have shown that plasma concentrations of OCS-FAs are associated with lower disease risk, although the mechanism responsible for this is debated. One possible mechanism for the endogenous production of OCS-FAs is α-oxidation, involving the activation, then hydroxylation of the α-carbon, followed by the removal of the terminal carboxyl group. Differentiation human adipocytes showed a distinct increase in the concentration of OCS-FAs, which was possibly caused through α-oxidation. Further evidence for an endogenous pathway, is in human plasma, where the ratio of C15:0 to C17:0 is approximately 1:2 which is contradictory to the expected levels of C15:0 to C17:0 roughly 2:1 as detected in dairy fat. We review the literature on the dietary consumption of OCS-FAs and their potential endogenous metabolism. Full article

(This article belongs to the Section Metabolites)

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30 pages, 1282 KiB

Open AccessReview

Volatile Compounds of Raspberry Fruit: From Analytical Methods to Biological Role and Sensory Impact

by Eugenio Aprea^*

, Franco Biasioli

and Flavia Gasperi

Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, 38010 San Michele all'Adige (TN), Italy

Molecules 2015, 20(2), 2445-2474; https://doi.org/10.3390/molecules20022445 - 30 Jan 2015

Cited by 83 | Viewed by 14811

Abstract

Volatile compounds play a key role in the formation of the well-recognized and widely appreciated raspberry aroma. Studies on the isolation and identification of volatile compounds in raspberry fruit (Rubus idaeus L.) are reviewed with a focus on aroma-related compounds. A table [...] Read more.

Volatile compounds play a key role in the formation of the well-recognized and widely appreciated raspberry aroma. Studies on the isolation and identification of volatile compounds in raspberry fruit (Rubus idaeus L.) are reviewed with a focus on aroma-related compounds. A table is drawn up containing a comprehensive list of the volatile compounds identified so far in raspberry along with main references and quantitative data where available. Two additional tables report the glycosidic bond and enantiomeric distributions of the volatile compounds investigated up to now in raspberry fruit. Studies on the development and evolution of volatile compounds during fruit formation, ripening and senescence, and genetic and environmental influences are also reviewed. Recent investigations showing the potential role of raspberry volatile compounds in cultivar differentiation and fruit resistance to mold disease are reported as well. Finally a summary of research done so far and our vision for future research lines are reported. Full article

(This article belongs to the Special Issue Aromas and Volatiles of Fruits)

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17 pages, 3221 KiB

Open AccessReview

Emerging Structural Insights into Glycoprotein Quality Control Coupled with N-Glycan Processing in the Endoplasmic Reticulum

by Tadashi Satoh^1,2,*, Takumi Yamaguchi^1,3 and Koichi Kato^1,3,*

¹ Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

² JST, PRESTO, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

³ Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan

Molecules 2015, 20(2), 2475-2491; https://doi.org/10.3390/molecules20022475 - 30 Jan 2015

Cited by 37 | Viewed by 10596

Abstract

In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc₃Man₉GlcNAc₂). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. [...] Read more.

In the endoplasmic reticulum (ER), the sugar chain is initially introduced onto newly synthesized proteins as a triantennary tetradecasaccharide (Glc₃Man₉GlcNAc₂). The attached oligosaccharide chain is subjected to stepwise trimming by the actions of specific glucosidases and mannosidases. In these processes, the transiently expressed N-glycans, as processing intermediates, function as signals for the determination of glycoprotein fates, i.e., folding, transport, or degradation through interactions of a series of intracellular lectins. The monoglucosylated glycoforms are hallmarks of incompletely folded states of glycoproteins in this system, whereas the outer mannose trimming leads to ER-associated glycoprotein degradation. This review outlines the recently emerging evidence regarding the molecular and structural basis of this glycoprotein quality control system, which is regulated through dynamic interplay among intracellular lectins, glycosidases, and glycosyltransferase. Structural snapshots of carbohydrate-lectin interactions have been provided at the atomic level using X-ray crystallographic analyses. Conformational ensembles of uncomplexed triantennary high-mannose-type oligosaccharides have been characterized in a quantitative manner using molecular dynamics simulation in conjunction with nuclear magnetic resonance spectroscopy. These complementary views provide new insights into glycoprotein recognition in quality control coupled with N-glycan processing. Full article

(This article belongs to the Special Issue Lectins)

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18 pages, 752 KiB

Open AccessArticle

Production and Characterization of Cosmetic Nanoemulsions Containing Opuntia ficus-indica (L.) Mill Extract as Moisturizing Agent

by Renato Cesar de Azevedo Ribeiro¹, Stella Maria Andrade Gomes Barreto¹, Elissa Arantes Ostrosky¹, Pedro Alves da Rocha-Filho²

, Lourena Mafra Veríssimo¹ and Márcio Ferrari^1,*

¹ College of Pharmacy, Federal University of Rio Grande do Norte, Rua Gustavo Cordeiro de Farias, s/n, Petrópolis, Natal 59012-570, RN, Brazil

² College of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida Zeferino Vaz, s/n, Monte Alegre, Ribeirão Preto 14040-903, SP, Brazil

Molecules 2015, 20(2), 2492-2509; https://doi.org/10.3390/molecules20022492 - 2 Feb 2015

Cited by 182 | Viewed by 13676

Abstract

This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% [...] Read more.

This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% of xanthan gum and 1% of Opuntia ficus-indica Mill extract (FXE) were white, homogeneous and fluid in aspect. Both formulations were stable during preliminary and accelerated stability tests. FX and FXE presented a pH compatible to skin pH (4.5–6.0); droplet size varying from 92.2 to 233.6 nm; a polydispersion index (PDI) around 0.200 and a zeta potential from −26.71 to −47.01 mV. FXE was able to increase the water content of the stratum corneum for 5 h after application on the forearm. The O/W nanoemulsions containing 1% of Opuntia ficus-indica (L.) Mill extract presented suitable stability for at least for 60 days. Besides, this formulation was able to increase the water content of stratum corneum, showing its moisturizing efficacy. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 1128 KiB

Open AccessReview

The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity

by Clara Iannuzzi, Gaetano Irace and Ivana Sirangelo^*

Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università di Napoli, Via L. De Crecchio 7, Napoli 80138, Italy

Molecules 2015, 20(2), 2510-2528; https://doi.org/10.3390/molecules20022510 - 2 Feb 2015

Cited by 99 | Viewed by 13561

Abstract

Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid [...] Read more.

Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)

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7 pages, 759 KiB

Open AccessArticle

Propane Dehydrogenation Catalyzed by ZSM-5 Zeolites. A Mechanistic Study Based on the Selective Energy Transfer (SET) Theory

by Ragnar Larsson

Chemical Engineering II, University of Lund, P.O. Box 124, SE-22100 Lund, Sweden

Molecules 2015, 20(2), 2529-2535; https://doi.org/10.3390/molecules20022529 - 2 Feb 2015

Cited by 10 | Viewed by 5693

Abstract

Experimentally determined activation energies of propane dehydrogenation catalyzed by ZSM-5 zeolites have been used to test the SET theory. The basis of this theory is that the catalyst system transfers vibrational energy via a resonance process to a specific vibration mode of the [...] Read more.

Experimentally determined activation energies of propane dehydrogenation catalyzed by ZSM-5 zeolites have been used to test the SET theory. The basis of this theory is that the catalyst system transfers vibrational energy via a resonance process to a specific vibration mode of the reacting molecule. Being excited up to a certain number of vibrational quanta the molecule is brought to reaction. By analyzing the above-mentioned activation energies we found the wave number of this “specific mode” to be 1065 cm⁻¹. This is very close to the rocking vibration of propane (1053 cm⁻¹). We suggest that the propane molecule reacts when excited so that the CH₃ group has been forced towards a flat structure with a carbon atom hybridization that is more sp² than sp³. Consequently there is no way for three H-atoms to bind to the carbon and one of them must leave. This is the starting point of the reaction. The isokinetic temperature of the system was found as T_iso = 727 ± 4 K. From the SET formula for T_iso when both energy-donating (ω) and energy-accepting (ν) vibrations have the same frequency, viz., T_iso = Nhcν/2R, we obtain ν = ω = 1011 ± 6 cm⁻¹. This agrees rather well with the CH₃ rocking mode (1053 cm⁻¹) and also with asymmetric “TO₄” stretching vibrations of the zeolite structure (ω). Full article

(This article belongs to the Special Issue Zeolite Chemistry)

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19 pages, 951 KiB

Open AccessArticle

Promoting Effect of Foliage Sprayed Zinc Sulfate on Accumulation of Sugar and Phenolics in Berries of Vitis vinifera cv. Merlot Growing on Zinc Deficient Soil

by Chang-Zheng Song¹, Mei-Ying Liu¹, Jiang-Fei Meng¹, Ming Chi¹, Zhu-Mei Xi^1,2,* and Zhen-Wen Zhang^1,2,*

¹ College of Enology, Northwest A&F University, Yangling 712100, Shaanxi, China

² Shaanxi Engineering Research Center for Viti-Viniculture, Yangling 712100, Shaanxi, China

Molecules 2015, 20(2), 2536-2554; https://doi.org/10.3390/molecules20022536 - 2 Feb 2015

Cited by 87 | Viewed by 8456

Abstract

The effect of foliage sprayed zinc sulfate on berry development of Vitis vinifera cv. Merlot growing on arid zone Zn-deficient soils was investigated over two consecutive seasons, 2013 and 2014. Initial zinc concentration in soil and vines, photosynthesis at three berry developmental stages, [...] Read more.

The effect of foliage sprayed zinc sulfate on berry development of Vitis vinifera cv. Merlot growing on arid zone Zn-deficient soils was investigated over two consecutive seasons, 2013 and 2014. Initial zinc concentration in soil and vines, photosynthesis at three berry developmental stages, berry weight, content of total soluble solids, titratable acidity, phenolics and expression of phenolics biosynthetic pathway genes throughout the stages were measured. Foliage sprayed zinc sulfate showed promoting effects on photosynthesis and berry development of vines and the promotion mainly occurred from veraison to maturation. Zn treatments enhanced the accumulation of total soluble solids, total phenols, flavonoids, flavanols, tannins and anthocyanins in berry skin, decreasing the concentration of titratable acidity. Furthermore, foliage sprayed zinc sulfate could significantly influence the expression of phenolics biosynthetic pathway genes throughout berry development, and the results of expression analysis supported the promotion of Zn treatments on phenolics accumulation. This research is the first comprehensive and detailed study about the effect of foliage sprayed Zn fertilizer on grape berry development, phenolics accumulation and gene expression in berry skin, providing a basis for improving the quality of grape and wine in Zn-deficient areas. Full article

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

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21 pages, 866 KiB

Open AccessArticle

Synthesis and Antioxidant Activity of Polyhydroxylated trans-Restricted 2-Arylcinnamic Acids

by Mitko Miliovsky¹, Ivan Svinyarov¹, Elena Prokopova², Daniela Batovska², Simeon Stoyanov² and Milen G. Bogdanov^1,*

¹ Faculty of Chemistry and Pharmacy, University of Sofia "St. Kliment. Ohridski", 1, James Bourchier Blvd., Sofia 1164, Bulgaria

² Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev Str. Bl. 9, Sofia 1113, Bulgaria

Molecules 2015, 20(2), 2555-2575; https://doi.org/10.3390/molecules20022555 - 2 Feb 2015

Cited by 12 | Viewed by 6965

Abstract

A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3a–p were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr₃. The structure of the newly synthesized compounds was confirmed by [...] Read more.

A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3a–p were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr₃. The structure of the newly synthesized compounds was confirmed by spectroscopic methods and the configuration around the double bond was unequivocally estimated by means of gated decoupling ¹³C-NMR spectra. It was shown that the trans-cinnamic acid fragment incorporated into the target compounds’ structure ensures the cis-configuration of the stilbene backbone and prevents further isomerization along the carbon–carbon double bond. The antioxidant activity of compounds 3a–p was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH^●), hydroxyl (OH^●) and superoxide (O₂^●^▬) radicals. The results obtained showed that the tested compounds possess higher activities than natural antioxidants such as protocatechuic acid, caffeic acid and gallic acid. Moreover, it was shown that a combination of two different and independently acting fragments of well-known pharmacological profiles into one covalently bonded hybrid molecule evoke a synergistic effect resulting in higher than expected activity. To rationalize the apparent antioxidant activity and to establish the mechanism of action, a SAR analysis and DFT quantum chemical computations were also performed. Full article

(This article belongs to the Special Issue Cinnamic Acids Hybrids with Biological Interest)

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15 pages, 1108 KiB

Open AccessArticle

Anti-Tuberculous Activity of Treponemycin Produced by a Streptomyces Strain MS-6-6 Isolated from Saudi Arabia

by Mahmoud A. Yassien^1,2,*, Hossam M. Abdallah^1,3

, Ali M. El-Halawany^1,3 and Asif A. M. Jiman-Fatani⁴

¹ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia

² Department of Microbiology and Immunology, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt

³ Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt

⁴ Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia

Molecules 2015, 20(2), 2576-2590; https://doi.org/10.3390/molecules20022576 - 2 Feb 2015

Cited by 16 | Viewed by 5637

Abstract

A Streptomyces strain MS-6-6 with promising anti-tuberculous activity was isolated from soil samples in Saudi Arabia. The nucleotide sequence of its 16S rRNA gene (1426 bp) evidenced a 100% similarity to Streptomyces mutabilis. Through an anti-tuberculous activity-guided approach, a polyketide macrolide was [...] Read more.

A Streptomyces strain MS-6-6 with promising anti-tuberculous activity was isolated from soil samples in Saudi Arabia. The nucleotide sequence of its 16S rRNA gene (1426 bp) evidenced a 100% similarity to Streptomyces mutabilis. Through an anti-tuberculous activity-guided approach, a polyketide macrolide was isolated and identified as treponemycin (TP). The structure of the isolated compound was determined by comprehensive analyses of its 1D and 2D NMR as well as HRESI-MS. In addition to the promising anti-tuberculous activity (MIC = 13.3 µg/mL), TP showed broad spectrum of activity against the Gram positive, Gram negative strains, and Candida albicans. Improvement of TP productivity (150%) was achieved through modification in liquid starch nitrate medium by replacing KNO₃ with corn steep liquor and yeast extract or tryptone, and removing CaCO₃ and K₂HPO₄. The follow up of TP percentage as well as its metabolites profile for each media was assessed by LC/DAD/MS. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 1257 KiB

Open AccessArticle

Synthesis of Novel Triazoles, Tetrazine, Thiadiazoles and Their Biological Activities

by Mohammed A. Al-Omair¹, Abdelwahed R. Sayed^1,2,* and Magdy M. Youssef^1,3

¹ Department of Chemistry, Faculty of Science, King Faisal University, Hofuf 31982, Saudi Arabia

² Department of Chemistry, Faculty of Science, University of Beni Suef, Beni Suef 62511, Egypt

³ Department of Chemistry, Faculty of Science, Mansoura University, Mansoura 35516, Egypt

Molecules 2015, 20(2), 2591-2610; https://doi.org/10.3390/molecules20022591 - 2 Feb 2015

Cited by 41 | Viewed by 8392

Abstract

An expedient synthesis of novel triazoles, tetrazine and thiadiazoles, using conveniently accessible and commercially available starting materials has been achieved. The synthesized compounds were characterized by spectroscopic and elemental analyses, and screened for their antibacterial activities against four different strains, namely E. coli [...] Read more.

An expedient synthesis of novel triazoles, tetrazine and thiadiazoles, using conveniently accessible and commercially available starting materials has been achieved. The synthesized compounds were characterized by spectroscopic and elemental analyses, and screened for their antibacterial activities against four different strains, namely E. coli, P. aeruginosa, S. aureus and B. megaterium. In particular, the compounds 5, 24 and 26h exhibited excellent antibacterial activities compared to the reference antibiotic. To get further insight about their behavior, these compounds were tested for their antioxidant activities via SOD-like activity, DPPH free radical scavenging activity, ABST and NO, which showed promising results. Furthermore, these compounds effectively promoted the cleavage of genomic DNA as well, in the absence of any external additives. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 1057 KiB

Open AccessArticle

A Study on the Application of Near Infrared Hyperspectral Chemical Imaging for Monitoring Moisture Content and Water Activity in Low Moisture Systems

by Eva Achata, Carlos Esquerre

, Colm O'Donnell and Aoife Gowen^*

School of Biosystems Engineering, University College Dublin, Dublin 4, Ireland

Molecules 2015, 20(2), 2611-2621; https://doi.org/10.3390/molecules20022611 - 3 Feb 2015

Cited by 40 | Viewed by 7473

Abstract

Moisture content and water activity are key parameters in predicting the stability of low moisture content products. However, conventional methods for moisture content and water activity determination (e.g., loss on drying method, ‎Karl Fischer titration, dew point method) are time consuming, demand specialized [...] Read more.

Moisture content and water activity are key parameters in predicting the stability of low moisture content products. However, conventional methods for moisture content and water activity determination (e.g., loss on drying method, ‎Karl Fischer titration, dew point method) are time consuming, demand specialized equipment and are not amenable to online processing. For this reason they are typically applied at-line on a limited number of samples. Near infrared hyperspectral chemical imaging is an emerging technique for spatially characterising the spectral properties of samples. Due to the fast acquisition of chemical images, many samples can be evaluated simultaneously, thus providing the potential for online evaluation of samples during processing. In this study, the potential of NIR chemical imaging for predicting the moisture content and water activity of a selection of low moisture content food systems is evaluated. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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14 pages, 1476 KiB

Open AccessArticle

Selective Reduction of Cr(VI) in Chromium, Copper and Arsenic (CCA) Mixed Waste Streams Using UV/TiO₂ Photocatalysis

by Shan Zheng¹, Wenjun Jiang¹, Mamun Rashid¹, Yong Cai¹, Dionysios D. Dionysiou² and Kevin E. O'Shea^1,*

¹ Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA

² Environmental Engineering and Science Program, University of Cincinnati, Cincinnati, OH 45221-0012, USA

Molecules 2015, 20(2), 2622-2635; https://doi.org/10.3390/molecules20022622 - 3 Feb 2015

Cited by 36 | Viewed by 8108

Abstract

The highly toxic Cr(VI) is a critical component in the Chromated Copper Arsenate (CCA) formulations extensively employed as wood preservatives. Remediation of CCA mixed waste and discarded treated wood products is a significant challenge. We demonstrate that UV/TiO₂ photocatalysis effectively reduces Cr(VI) [...] Read more.

The highly toxic Cr(VI) is a critical component in the Chromated Copper Arsenate (CCA) formulations extensively employed as wood preservatives. Remediation of CCA mixed waste and discarded treated wood products is a significant challenge. We demonstrate that UV/TiO₂ photocatalysis effectively reduces Cr(VI) to less toxic Cr(III) in the presence of arsenate, As(V), and copper, Cu(II). The rapid conversion of Cr(VI) to Cr(III) during UV/TiO₂ photocatalysis occurs over a range of concentrations, solution pH and at different Cr:As:Cu ratios. The reduction follows pseudo-first order kinetics and increases with decreasing solution pH. Saturation of the reaction solution with argon during UV/TiO₂ photocatalysis had no significant effect on the Cr(VI) reduction demonstrating the reduction of Cr(VI) is independent of dissolved oxygen. Reduction of Cu(II) and As(V) does not occur under the photocatalytic conditions employed herein and the presence of these two in the tertiary mixtures had a minimal effect on Cr(VI) reduction. The Cr(VI) reduction was however, significantly enhanced by the addition of formic acid, which can act as a hole scavenger and enhance the reduction processes initiated by the conduction band electron. Our results demonstrate UV/TiO₂ photocatalysis effectively reduces Cr(VI) in mixed waste streams under a variety of conditions. Full article

(This article belongs to the Special Issue Photocatalysis)

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22 pages, 2335 KiB

Open AccessArticle

Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice

by Fernando P. Conte^1,†

, Fausto K. Ferraris^1,†

, Thadeu E. M. M. Costa¹, Patricia Pacheco¹, Leonardo N. Seito¹, Waldiceu A. Verri, Jr.^2,3, Fernando Q. Cunha³, Carmen Penido^1,4,‡ and Maria G. Henriques^1,4,*,‡

¹ Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil

² Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Brazil

³ Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil

⁴ Centro de Desenvolvimento Tecnológico em Saúde, CDTS/INCT-IDN, Fundação Oswaldo Cruz, Rio de Janeiro 21045-360, Brazil

^† These authors contributed equally to this work.

^‡ These authors are considered last authors.

Molecules 2015, 20(2), 2636-2657; https://doi.org/10.3390/molecules20022636 - 3 Feb 2015

Cited by 23 | Viewed by 8276

Abstract

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; [...] Read more.

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005–5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB₄, PGE₂, TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations. Full article

(This article belongs to the Collection Bioactive Compounds)

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10 pages, 690 KiB

Open AccessArticle

A Study of the Geo-Herbalism of Evodiae Fructus Based on a Flow-Injection Mass Spectrometric Fingerprinting Method Combined with Chemometrics

by Yang Zhao^1,2, Xin Zhou^1,2,*, Yun-Ling Zhao^1,2, Xiao-Jian Gong^1,2 and Chao Zhao^1,2

¹ Key Laboratory for Information System of Mountainous Areas and Protection of Ecological Environment, Guizhou Normal University, Guiyang 550001, China

² The Research Center for Quality Control of Natural Medicine, Guizhou Normal University, Guiyang 550001, China

Molecules 2015, 20(2), 2658-2667; https://doi.org/10.3390/molecules20022658 - 3 Feb 2015

Cited by 9 | Viewed by 6125

Abstract

A flow-injection mass spectrometric (FIMS) fingerprinting method in combination with principal component analysis (PCA) was used to study the geo-herbalism of Evodiae Fructus (EF) samples. Twenty four EF samples from different regions in China were collected and analyzed. The PCA scores plot showed [...] Read more.

A flow-injection mass spectrometric (FIMS) fingerprinting method in combination with principal component analysis (PCA) was used to study the geo-herbalism of Evodiae Fructus (EF) samples. Twenty four EF samples from different regions in China were collected and analyzed. The PCA scores plot showed that the samples from Guizhou Province were scattered in different groups, however, most of the samples from other provinces were basically scattered in the same group. Nine characteristic compounds responsible for the classification of the samples were tentatively characterized. These nine compounds might help differentiating EF samples from different regions. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 819 KiB

Open AccessArticle

Synthesis and Evaluation of New 1,5-Diaryl-3-[4-(methyl-sulfonyl)phenyl]-4,5-dihydro-1H-pyrazole Derivatives as Potential Antidepressant Agents

by Ahmet Özdemir^1,*, Mehlika Dilek Altıntop^1,2, Zafer Asım Kaplancıklı¹

, Özgür Devrim Can³, Ümide Demir Özkay³ and Gülhan Turan-Zitouni¹

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

² Graduate School of Health Sciences, Anadolu University, 26470 Eskişehir, Turkey

³ Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

Molecules 2015, 20(2), 2668-2684; https://doi.org/10.3390/molecules20022668 - 4 Feb 2015

Cited by 72 | Viewed by 6491

Abstract

In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2a–s were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were [...] Read more.

In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2a–s were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were also investigated using an activity cage apparatus. Among these derivatives, compounds 2b, 2d, 2f, 2o, and 2r decreased both horizontal and vertical activity number of the mice. On the other hand, compounds 2a, 2h, 2j, 2k, 2l, 2m, and 2n, which did not induce any significant change in the locomotor activity, significantly shortened the immobility time of mice in TST and MFST, representing the presence of the antidepressant-like effect. Additionally, the same compounds increased the swimming time of mice in MFST without any change in climbing duration, similar to the reference drug fluoxetine (10 mg/kg). In the light of previous papers examining the effects of pyrazolines on central nervous system, this study, once more, pointed out remarkable antidepressant activity potential of pyrazoline derivatives. Full article

(This article belongs to the Section Medicinal Chemistry)

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8 pages, 664 KiB

Open AccessArticle

Development and Characterization of Polymorphic Microsatellite Markers (SSRs) for an Endemic Plant, Pseudolarix amabilis (Nelson) Rehd. (Pinaceae)

by Qi-Fang Geng^1,2,†, Jun Liu^1,2,†, Lin Sun^1,2, Hong Liu^3,4, Yan Ou-Yang^1,2, Ying Cai^1,2, Xin-Sheng Tang⁵, Hong-Wei Zhang⁶, Zhong-Sheng Wang^1,2,* and Shu-Qing An^1,2,*

¹ School of Life Science, Nanjing University, Nanjing 210093, China

² State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, China

³ International Center for Tropical Botany, Department of Earth and Environment, Florida International University, Miami, FL 33199, USA

⁴ College of Forestry, Guangxi University, Nanning 530004, China

⁵ College of Life and Environment Sciences, Huangshan University, Huangshan 245041, China

⁶ Administration of Zhejiang Qingliangfeng National Nature Reserve, Lin'an 311321, China

^† These authors are equally contributed to this work.

Molecules 2015, 20(2), 2685-2692; https://doi.org/10.3390/molecules20022685 - 4 Feb 2015

Cited by 6 | Viewed by 6429

Abstract

Pseudolarix (Pinaceae) is a vulnerable (sensu IUCN) monotypic genus restricted to southeastern China. To better understand levels of genetic diversity, population structure and gene flow among populations of P. amabilis, we developed five compound SSR markers and ten novel polymorphic expressed sequence [...] Read more.

Pseudolarix (Pinaceae) is a vulnerable (sensu IUCN) monotypic genus restricted to southeastern China. To better understand levels of genetic diversity, population structure and gene flow among populations of P. amabilis, we developed five compound SSR markers and ten novel polymorphic expressed sequence tags (EST) derived microsatellites. The results showed that all 15 loci were polymorphic with the number of alleles per locus ranging from two to seven. The expected and observed heterozygosities varied from 0.169 to 0.752, and 0.000 to 1.000, respectively. The inbreeding coefficient ranged from −0.833 to 1.000. These markers will contribute to research on genetic diversity and population genetic structure of P. amabilis, which in turn will contribute to the species conservation. Full article

(This article belongs to the Section Molecular Diversity)

14 pages, 996 KiB

Open AccessArticle

Silver Nanoparticles Biosynthesized Using Achillea biebersteinii Flower Extract: Apoptosis Induction in MCF-7 Cells via Caspase Activation and Regulation of Bax and Bcl-2 Gene Expression

by Javad Baharara^1,2, Farideh Namvar^1,3,*, Tayebe Ramezani⁴, Marzieh Mousavi¹ and Rosfarizan Mohamad^3,5

¹ Research Center for Animal Development Applied Biology, Mashhad Branch, Islamic Azad University, Mashhad 917568, Iran

² Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad 917568, Iran

³ Institute of Tropical Forestry and Forest Products (INTROP), Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

⁴ Faculty of Biological Sciences, Kharazmi University, Tehran 14911, Iran

⁵ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

Molecules 2015, 20(2), 2693-2706; https://doi.org/10.3390/molecules20022693 - 5 Feb 2015

Cited by 152 | Viewed by 11062

Abstract

Silver nanoparticles (Ag-NPs), the most popular nanoparticles, possess unique properties. Achillea biebersteinii is a plant of the Asteraceae family rich in active antitumor components. The aim of this research was the characterization and investigation of the cytotoxic properties of Ag-NPs synthesized using A. [...] Read more.

Silver nanoparticles (Ag-NPs), the most popular nanoparticles, possess unique properties. Achillea biebersteinii is a plant of the Asteraceae family rich in active antitumor components. The aim of this research was the characterization and investigation of the cytotoxic properties of Ag-NPs synthesized using A. biebersteinii flower extract, on a human breast cancer cell line. The Ag-NPs were synthesized after approximately 180 min of reaction at 40 °C, then they were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The anti-apoptosis effect of Ag-NPs on the MCF-7 cell line was investigated by MTT assay, DAPI and acridine orange staining and caspase activity. The transcriptional expression of bax, bcl-2, caspase-3, -8 and -9 were also evaluated by RT-PCR. The TEM images revealed that the Ag-NPs morphology had a different shape. The DLS indicated that the average hydrodynamic diameter of the biosynthesized Ag-NPs was around 12 nm. By UV-visible spectroscopy the strongest absorbance peak was observed at 460 nm. The FTIR results also showed interaction between the plant extract and Ag-NPs due to the similarity in the peak patterns. The EDS results showed that Ag-NPs display an absorption peak at 3 keV, indicating the presence of the element silver. The Ag-NPs caused a dose-dependent decrease in cell viability, fragmentation in nucleic acid, inhibited the proliferation and induction of apoptosis on MCF-7 by suppressing specific cell cycle genes, and simulation programmed cell dead genes. Further investigation is required to establish the potential of this novel and promising approach in cancer therapy. Full article

(This article belongs to the Section Organic Chemistry)

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21 pages, 797 KiB

Open AccessReview

Diversity of Heparan Sulfate and HSV Entry: Basic Understanding and Treatment Strategies

by Vaibhav Tiwari^1,2,*, Morgan S. Tarbutton¹ and Deepak Shukla^2,3

¹ Department of Microbiology & Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA

² Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA

³ Department of Microbiology & Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA

Molecules 2015, 20(2), 2707-2727; https://doi.org/10.3390/molecules20022707 - 5 Feb 2015

Cited by 46 | Viewed by 11453

Abstract

A modified form of heparan sulfate (HS) known as 3-O-sulfated heparan sulfate (3-OS HS) generates fusion receptor for herpes simplex virus (HSV) entry and spread. Primary cultures of corneal fibroblasts derived from human eye donors have shown the clinical [...] Read more.

A modified form of heparan sulfate (HS) known as 3-O-sulfated heparan sulfate (3-OS HS) generates fusion receptor for herpes simplex virus (HSV) entry and spread. Primary cultures of corneal fibroblasts derived from human eye donors have shown the clinical significance of this receptor during HSV corneal infection. 3-OS HS- is a product of a rare enzymatic modification at C3 position of glucosamine residue which is catalyzed by 3-O-sulfotransferases (3-OSTs) enzymes. From humans to zebrafish, the 3-OST enzymes are highly conserved and widely expressed in cells and tissues. There are multiple forms of 3-OSTs each producing unique subset of sulfated HS making it chemically diverse and heterogeneous. HSV infection of cells or zebrafish can be used as a unique tool to understand the structural-functional activities of HS and 3-OS HS and likewise, the infection can be used as a functional assay to screen phage display libraries for identifying HS and 3-OS HS binding peptides or small molecule inhibitors. Using this approach over 200 unique 12-mer HS and 3-OS HS recognizing peptides were isolated and characterized against HSV corneal infection where 3-OS HS is known to be a key receptor. In this review we discuss emerging role of 3-OS HS based therapeutic strategies in preventing viral infection and tissue damage. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Their Mimetics)

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42 pages, 3236 KiB

Open AccessReview

The Multifaceted Role of Curcumin in Cancer Prevention and Treatment

by Muthu K. Shanmugam¹, Grishma Rane^1,2, Madhu Mathi Kanchi², Frank Arfuso³, Arunachalam Chinnathambi⁴, M. E. Zayed⁴, Sulaiman Ali Alharbi⁴, Benny K. H. Tan¹, Alan Prem Kumar^1,2,3,5,*

and Gautam Sethi^1,3,4,*

¹ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore

² Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore 117599, Singapore

³ School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia

⁴ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

⁵ Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA

Molecules 2015, 20(2), 2728-2769; https://doi.org/10.3390/molecules20022728 - 5 Feb 2015

Cited by 443 | Viewed by 53079

Abstract

Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also [...] Read more.

Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also expensive. Thus identification of pharmacological agents that do not have these disadvantages is required. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa), is one such agent that has been extensively studied over the last three to four decades for its potential anti-inflammatory and/or anti-cancer effects. Curcumin has been found to suppress initiation, progression, and metastasis of a variety of tumors. These anti-cancer effects are predominantly mediated through its negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. It also abrogates proliferation of cancer cells by arresting them at different phases of the cell cycle and/or by inducing their apoptosis. The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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5 pages, 623 KiB

Open AccessEditorial

Phytoalexins: Current Progress and Future Prospects

by Philippe Jeandet

Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France

Molecules 2015, 20(2), 2770-2774; https://doi.org/10.3390/molecules20022770 - 5 Feb 2015

Cited by 84 | Viewed by 12023

Abstract

Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins [...] Read more.

Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins started with progress in their biochemistry and bio-organic chemistry, resulting in the determination of their structure, their biological activity, as well as mechanisms of their synthesis and catabolism by microorganisms. Elucidation of the biosynthesis of numerous phytoalexins also permitted the use of molecular biology tools for the exploration of the genes encoding enzymes of their synthesis pathways and their regulators. This has led to potential applications for increasing plant resistance to diseases. Phytoalexins display an enormous diversity belonging to various chemical families such as for instance, phenolics, terpenoids, furanoacetylenes, steroid glycoalkaloids, sulfur-containing compounds and indoles.[...] Full article

(This article belongs to the Special Issue Phytoalexins: Current Progress and Future Prospects)

11 pages, 2936 KiB

Open AccessArticle

The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides

by Gabriela A. Eggimann¹, Kathryn Sweeney¹, Hannah L. Bolt¹, Neshat Rozatian¹, Steven L. Cobb^1,* and Paul W. Denny^1,2,*

¹ Biophysical Sciences Institute, Department of Chemistry and School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK

² School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees TS17 6BH, UK

Molecules 2015, 20(2), 2775-2785; https://doi.org/10.3390/molecules20022775 - 6 Feb 2015

Cited by 27 | Viewed by 8388

Abstract

Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that the mammalian pathogenic amastigote form of L. mexicana, a causative [...] Read more.

Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that the mammalian pathogenic amastigote form of L. mexicana, a causative agent of cutaneous leishmaniasis, is resistant to the amphibian-derived temporin family of AMPs when compared to the insect stage promastigote form. The mode of resistance is unknown, however the insect and mammalian stages of Leishmania possess radically different cell surface coats, with amastigotes displaying low (or zero) quantities of lipophosphoglycan (LPG) and proteophosphoglycan (PPG), macromolecules which form thick a glycocalyx in promastigotes. It has been predicted that negatively charged LPG and PPG influence the sensitivity/resistance of promastigote forms to cationic temporins. Using LPG and PPG mutant L. mexicana, and an extended range of temporins, in this study we demonstrated that whilst LPG has little role, PPG is a major factor in promastigote sensitivity to the temporin family of AMPs, possibly due to the conferred anionic charge. Therefore, the lack of PPG seen on the surface of pathogenic amastigote L. mexicana may be implicated in their resistance to these peptides. Full article

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

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16 pages, 3574 KiB

Open AccessArticle

Scopoletin Protects against Methylglyoxal-Induced Hyperglycemia and Insulin Resistance Mediated by Suppression of Advanced Glycation Endproducts (AGEs) Generation and Anti-Glycation

by Wen-Chang Chang¹, Shinn-Chih Wu², Kun-Di Xu¹, Bo-Chieh Liao¹, Jia-Feng Wu¹ and An-Sheng Cheng^1,*

¹ Department of Medicinal Plant Development, Yupintang Traditional Chinese Medicine Foundation, 4F., No.2, Ln. 138, Yongyuan Rd., Yonghe Dist., New Taipei City 234, Taiwan

² Department of Animal Science and Technology, National Taiwan University, 59 Roosevelt Road Section 4, Taipei 10617, Taiwan

Molecules 2015, 20(2), 2786-2801; https://doi.org/10.3390/molecules20022786 - 9 Feb 2015

Cited by 52 | Viewed by 10358

Abstract

Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the [...] Read more.

Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG) levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the positive regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2). In this study, we investigated the ability of scopoletin (SP) to protect against MG-induced hyperglycemia and insulin resistance. Recently, SP was shown to be a peroxisome proliferator-activated receptor-γ activator to elevate insulin sensitivity. We investigated the effects of oral administration of SP on the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats to understand the potential mechanism of scopoletin for diabetes protection. Our results suggested that SP activated Nrf2 by Ser40 phosphorylation, resulting in the metabolism of MG into d-lactic acid and the inhibition of AGEs generation, which reduced the accumulation of AGEs in the livers of MG-induced rats. In this manner, SP improved the results of the oral glucose tolerance test and dyslipidemia. Moreover, SP also increased the plasma translocation of glucose transporter-2 and promoted Akt phosphorylation caused by insulin treatment in MG-treated FL83B hepatocytes. In contrast, SP effectively suppressed protein tyrosine phosphatase 1B (PTP1B) expression, thereby alleviating insulin resistance. These findings suggest that SP acts as an anti-glycation and anti-diabetic agent, and thus has therapeutic potential for the prevention of diabetes. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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14 pages, 685 KiB

Open AccessReview

Entamoeba histolytica: Adhesins and Lectins in the Trophozoite Surface

by Magdalena Aguirre García, Laila Gutiérrez-Kobeh and Rosario López Vancell^*

Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis #148, Col. Doctores, C.P. 06726 Mexico, D.F., Mexico

Molecules 2015, 20(2), 2802-2815; https://doi.org/10.3390/molecules20022802 - 9 Feb 2015

Cited by 29 | Viewed by 9333

Abstract

Entamoeba histolytica is the causative agent of amebiasis in humans and is responsible for 100,000 deaths annually, making it the third leading cause of death due to a protozoan parasite. Pathogenesis appears to result from the potent cytotoxic activity of the parasite, which [...] Read more.

Entamoeba histolytica is the causative agent of amebiasis in humans and is responsible for 100,000 deaths annually, making it the third leading cause of death due to a protozoan parasite. Pathogenesis appears to result from the potent cytotoxic activity of the parasite, which kills host cells within minutes. Although the mechanism is unknown, it is well established to be contact-dependent. The life cycle of the parasite alternates with two forms: the resistant cyst and the invasive trophozoite. The adhesive interactions between the parasite and surface glycoconjugates of host cells, as well as those lining the epithelia, are determinants for invasion of human tissues, for its cytotoxic activity, and finally for the outcome of the disease. In this review we present an overview of the information available on the amebic lectins and adhesins that are responsible of those adhesive interactions and we also refer to their effect on the host immune response. Finally, we present some concluding remarks and perspectives in the field. Full article

(This article belongs to the Special Issue Lectins)

12 pages, 995 KiB

Open AccessCommunication

Novel Zinc-Catalytic Systems for Ring-Opening Polymerization of ε-Caprolactone

by Karolina Żółtowska^1,†, Marcin Sobczak^1,2,*,† and Ewa Olędzka¹

¹ Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, ul. Banacha 1, 02-097 Warsaw, Poland

² Chair of Chemistry, Department of Organic Chemistry, Faculty of Materials Science and Design, Kazimierz Pulaski University of Technology and Humanities in Radom, ul. Chrobrego 27, 26-600 Radom, Poland

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2816-2827; https://doi.org/10.3390/molecules20022816 - 9 Feb 2015

Cited by 39 | Viewed by 7390

Abstract

Polycaprolactone (PCL) is a biodegradable synthetic polymer that is currently widely used in many pharmaceutical and medical applications. In this paper we describe the coordination ring-opening polymerization of ε-caprolactone in the presence of two newly synthesized catalytic systems: diethylzinc/gallic acid and diethylzinc/propyl gallate. [...] Read more.

Polycaprolactone (PCL) is a biodegradable synthetic polymer that is currently widely used in many pharmaceutical and medical applications. In this paper we describe the coordination ring-opening polymerization of ε-caprolactone in the presence of two newly synthesized catalytic systems: diethylzinc/gallic acid and diethylzinc/propyl gallate. The chemical structures of the obtained PCLs were characterized by ¹H- or ¹³C-NMR, FTIR spectroscopy and MALDI TOF mass spectrometry. The average molecular weight of the resulting polyesters was analysed by gel permeation chromatography and a viscosity method. The effects of temperature, reaction time and type of catalytic system on the polymerization process were examined. Linear PCLs with defined average molecular weight were successfully obtained. Importantly, in some cases the presence of macrocyclic products was not observed during the polymerization process. This study provides an effective method for the synthesis of biodegradable polyesters for medical and pharmaceutical applications due to the fact that gallic acid/propyl gallate are commonly used in the pharmaceutical industry. Full article

(This article belongs to the Special Issue Ring-Opening Polymerization)

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3 pages, 768 KiB

Open AccessCorrection

Correction: Calderon, C.P. Data-Driven Techniques for Detecting Dynamical State Changes in Noisily Measured 3D Single-Molecule Trajectories. Molecules 19, 18381-18398

by Christopher P. Calderon

Ursa Analytics, Denver, CO 80212, USA

Molecules 2015, 20(2), 2828-2830; https://doi.org/10.3390/molecules20022828 - 9 Feb 2015

Viewed by 4976

Abstract

The author wishes to make the following corrections to paper [1] (doi:10.3390/molecules191118381, website: https://www.mdpi.com/1420-3049/19/11/18381): Full article

(This article belongs to the Special Issue Single Molecule Techniques)

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4 pages, 625 KiB

Open AccessEditorial

The Games Radicals Play: Special Issue on Free Radicals and Radical Ions

by John C. Walton^1,*,†

and Ffrancon Williams^2,*,†

¹ EaStCHEM School of Chemistry, University of St. Andrews, St. Andrews KY16 9ST, UK

² Department of Chemistry, University of Tennessee, Knoxville, TN 37996-1600, USA

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2831-2834; https://doi.org/10.3390/molecules20022831 - 9 Feb 2015

Cited by 1 | Viewed by 5824

Abstract

Chemistry and Physics have aptly been described as “most excellent children of Intellect and Art” [1]. Both these “children” engage with many playthings, and molecules rank as one of their first favorites, especially radicals, which are amongst the most lively and exciting. Checking [...] Read more.

Chemistry and Physics have aptly been described as “most excellent children of Intellect and Art” [1]. Both these “children” engage with many playthings, and molecules rank as one of their first favorites, especially radicals, which are amongst the most lively and exciting. Checking out radicals dancing to the music of entropy round their potential energy ballrooms is surely both entertaining and enlightening. Radicals’ old favorite convolutions are noteworthy, but the new styles, modes and arrangements appearing on the scene are even more interesting. Some of these are ephemeral and enjoy only a brief appearance, others are retro-types reappearing in new guises, still others are genuinely new and “go viral” in the scientific world. This Special Issue of Molecules contains the observations and reflections of a select group of chemists and physicists fascinated by this spectacle. It contains an eclectic mix reflecting on new modes and advances as well as on permutations and combinations that revive mature themes. [...] Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

2 pages, 592 KiB

Open AccessCorrection

Correction: El Azab, I.H., et al. Microwave-Assisted Synthesis of Novel 2H-Chromene Derivatives Bearing Phenylthiazolidinones and Their Biological Activity Assessment. Molecules 2014, 19, 19648-19664

by Islam H. El Azab^1,2,*

, Mohamed M. Youssef³ and Amin M. Amin^1,4

¹ Chemistry Department, Faculty of Science, Taif University, Al-Haweiah, P.O. Box 888, Taif 21974, Saudi Arabia

² Chemistry Department, Faculty of Science, Aswan University, Aswan 81528, Egypt

³ Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt

⁴ Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt

Molecules 2015, 20(2), 2835-2836; https://doi.org/10.3390/molecules20022835 - 9 Feb 2015

Viewed by 5344

Abstract

The authors wish to revise the Author Affiliation section of the title paper, published in Molecules [1], (doi:10.3390/molecules191219648, website: https://www.mdpi.com/1420-3049/19/12/19648). To recognize the fact that the research described was performed in part at the facilities of Taif University and to acknowledge that institution’s [...] Read more.

The authors wish to revise the Author Affiliation section of the title paper, published in Molecules [1], (doi:10.3390/molecules191219648, website: https://www.mdpi.com/1420-3049/19/12/19648). To recognize the fact that the research described was performed in part at the facilities of Taif University and to acknowledge that institution’s generous financial support[...] Full article

(This article belongs to the Section Organic Chemistry)

13 pages, 2682 KiB

Open AccessArticle

Solvent-Free Copper-Catalyzed Azide-Alkyne Cycloaddition under Mechanochemical Activation

by Laura Rinaldi^1,2, Katia Martina¹, Francesca Baricco¹, Laura Rotolo¹ and Giancarlo Cravotto^1,*

¹ Dipartimento di Scienza e Tecnologia del Farmaco and NIS—Centre for Nanostructured Interfaces and Surfaces, University of Turin, Via P. Giuria 9, Turin 10125, Italy

² Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, University of Turin, Via Quarello 15, Turin 10125, Italy

Molecules 2015, 20(2), 2837-2849; https://doi.org/10.3390/molecules20022837 - 9 Feb 2015

Cited by 62 | Viewed by 12275

Abstract

The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been [...] Read more.

The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been tested on a number of different substrates and in all cases afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yields and purities. The final compounds were isolated in almost quantitative overall yields after simple filtration, making this procedure facile and rapid. The optimized CuAAC protocol was efficiently applied even with bulky functionalized β-cyclodextrins (β-CD) and scaled-up to 10 g of isolated product. Full article

(This article belongs to the Collection Advances in Click Chemistry)

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7 pages, 679 KiB

Open AccessCommunication

New Cytotoxic Sesquiterpenoids from Siegesbeckia glabrescens

by Qian Wu^1,†, Hua Li^1,†, So Yoon Lee¹, Hwa Jin Lee^2,* and Jae-Ha Ryu^1,*

¹ Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Korea

² Department of Natural Medicine Resources, Semyung University, Chungbuk 390-711, Korea

^† These authors are equally contributed to this work.

Molecules 2015, 20(2), 2850-2856; https://doi.org/10.3390/molecules20022850 - 10 Feb 2015

Cited by 15 | Viewed by 5935

Abstract

Two new sesquiterpenoids, siegenolides A (1) and B (2), and two known sesquiterpenes 3 and 4 were isolated from Siegesbeckia glabrescens. Their structures were elucidated by spectroscopic analyses, and they were further evaluated for their cytotoxic activities against [...] Read more.

Two new sesquiterpenoids, siegenolides A (1) and B (2), and two known sesquiterpenes 3 and 4 were isolated from Siegesbeckia glabrescens. Their structures were elucidated by spectroscopic analyses, and they were further evaluated for their cytotoxic activities against human cancer cells (MCF-7, AsPC-1, SW480, HCT 116, HepG2, HeLa). Compounds 1–4 showed differential cytotoxic effects on the target cancer cells with IC₅₀ values in the range of 0.9–33.3 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 1151 KiB

Open AccessArticle

Ring-Opening Polymerization of ε-Caprolactone Initiated by Ganciclovir (GCV) for the Preparation of GCV-Tagged Polymeric Micelles

by Alicia J. Sawdon and Ching-An Peng^*

Department of Chemical Engineering, Michigan Technological University, Houghton, MI 49931, USA

Molecules 2015, 20(2), 2857-2867; https://doi.org/10.3390/molecules20022857 - 10 Feb 2015

Cited by 15 | Viewed by 7011

Abstract

Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this [...] Read more.

Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this study, guanosine-based GCV was used as the initiator directly in ring-opening polymerization of ε-caprolactone (ε-CL) to form hydrophobic GCV-poly(caprolactone) (GCV-PCL) which was then grafted with hydrophilic chitosan to form amphiphilic copolymers for the preparation of stable micellar nanoparticles. Successful synthesis of GCV-PCL and GCV-PCL-chitosan were verified by ¹H-NMR analysis. Self-assembled micellar nanoparticles were characterized by dynamic light scattering and zetasizer with an average size of 117 nm and a positive charge of 24.2 mV. The drug release kinetics of GCV was investigated and cytotoxicity assay demonstrated that GCV-tagged polymeric micelles were non-toxic. Our results showed that GCV could be used directly in the initiation of ring-opening polymerization of ε-CL and non-toxic polymeric micelles for GCV delivery can be formed. Full article

(This article belongs to the Special Issue Ring-Opening Polymerization)

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24 pages, 1170 KiB

Open AccessArticle

Distribution and Evolution of the Lectin Family in Soybean (Glycine max)

by Sofie Van Holle

and Els J. M. Van Damme^*

Laboratory of Biochemistry and Glycobiology, Department of Molecular Biotechnology, Ghent University, Coupure links 653, 9000 Ghent, Belgium

Molecules 2015, 20(2), 2868-2891; https://doi.org/10.3390/molecules20022868 - 11 Feb 2015

Cited by 41 | Viewed by 9679

Abstract

Lectins are a diverse group of proteins that bind specific carbohydrates and are found throughout all kingdoms. In plants, lectins are involved in a range of important processes such as plant defense and stress signaling. Although the genome sequence of Glycine max (soybean) [...] Read more.

Lectins are a diverse group of proteins that bind specific carbohydrates and are found throughout all kingdoms. In plants, lectins are involved in a range of important processes such as plant defense and stress signaling. Although the genome sequence of Glycine max (soybean) has been published, little is known about the abundance and expansion patterns of lectin genes in soybean. Using BLAST and hidden Markov models, a total of 359 putative lectin genes have been identified. Furthermore, these sequences could be classified in nine of the twelve plant lectin families identified today. Analysis of the domain organization demonstrated that most of the identified lectin genes encode chimerolectins, consisting of one or multiple lectin domains combined with other known protein domains. Both tandem and segmental duplication events have contributed to the expansion of the lectin gene family. These data provide a detailed understanding of the domain architecture and molecular evolution of the lectin gene family in soybean. Full article

(This article belongs to the Special Issue Lectins)

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11 pages, 1919 KiB

Open AccessArticle

Synthesis and Molecular Structure of the 5-Methoxycarbonylpentyl α-Glycoside of the Upstream, Terminal Moiety of the O-Specific Polysaccharide of Vibrio cholerae O1, Serotype Inaba

by Peng Xu¹, Edwin D. Stevens², Alfred D. French³ and Pavol Kováč^1,*

¹ NIDDK, LBC, National Institutes of Health, Bethesda, MD 20892-0815, USA

² Department of Chemistry, Western Kentucky University, 1906 College Heights Blvd., Bowling Green, KY 42101-1709, USA

³ Southern Regional Research Center, US Department of Agriculture, 1100 Robert E Lee Blvd, New Orleans, LA 70124, USA

Molecules 2015, 20(2), 2892-2902; https://doi.org/10.3390/molecules20022892 - 11 Feb 2015

Cited by 2 | Viewed by 5534

Abstract

The trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-α-d-mannopyranosyl trichloroacetimidate followed by a two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplén deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-α-D-mannopyranoside. The [...] Read more.

The trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-α-d-mannopyranosyl trichloroacetimidate followed by a two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplén deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-L-glycero-tetronamido)-4,6-dideoxy-α-D-mannopyranoside. The structure of the latter, for which crystals were obtained in the analytically pure state for the first time, followed from its NMR and high-resolution mass spectra and was confirmed by X-ray crystallography. The molecule has two approximately linear components; a line through the aglycon intersects a line through the mannosyl and tetronylamido groups at 120°. The crystal packing separates the aglycon groups from the tetronylamido and mannosyl groups, with only C-H…O hydrogen bonding among the aglycon groups and N-H…O, O-H…O and C-H…O links among the tetronylamido and mannosyl groups. A carbonyl oxygen atom accepts the strongest O-H…O hydrogen bond and two strong C-H…O hydrogen bonds. The geometric properties were compared with those of related molecules. Full article

(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)

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19 pages, 2917 KiB

Open AccessArticle

Enzymatic Hydrolysis of Oleuropein from Olea europea (Olive) Leaf Extract and Antioxidant Activities

by Jiao-Jiao Yuan^1,2,3,4, Cheng-Zhang Wang^1,2,3,4,*, Jian-Zhong Ye^1,2,3,4, Ran Tao^1,2,3,4 and Yu-Si Zhang^1,2,3,4

¹ Institute of Chemical Industry of Forest Products, CAF, Nanjing 210042, China

² Key and Open Laboratory on Forest Chemical Engineering, SFA, Nanjing 210042, China

³ Key Laboratory of Biomass Energy and Matetial, Nanjing 210042, China

⁴ Institute of New Technology of Forestry, CAF, Beijing 100091, China

Molecules 2015, 20(2), 2903-2921; https://doi.org/10.3390/molecules20022903 - 11 Feb 2015

Cited by 83 | Viewed by 14133

Abstract

Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are [...] Read more.

Oleuropein (OE), the main polyphenol in olive leaf extract, is likely to decompose into hydroxytyrosol (HT) and elenolic acid under the action of light, acid, base, high temperature. In the enzymatic process, the content of OE in olive leaf extract and enzyme are key factors that affect the yield of HT. A selective enzyme was screened from among 10 enzymes with a high OE degradation rate. A single factor (pH, temperature, time, enzyme quantity) optimization process and a Box-Behnken design were studied for the enzymatic hydrolysis of 81.04% OE olive leaf extract. Additionally, enzymatic hydrolysis results with different substrates (38.6% and 81.04% OE) were compared and the DPPH antioxidant properties were also evaluated. The result showed that the performance of hydrolysis treatments was best using hemicellulase as a bio-catalyst, and the high purity of OE in olive extract was beneficial to biotransform OE into HT. The optimal enzymatic conditions for achieving a maximal yield of HT content obtained by the regression were as follows: pH 5, temperature 55 °C and enzyme quantity 55 mg. The experimental result was 11.31% ± 0.15%, and the degradation rate of OE was 98.54%. From the present investigation of the antioxidant activity determined by the DPPH method, the phenol content and radical scavenging effect were both decreased after enzymatic hydrolysis by hemicellulase. However, a high antioxidant activity of the ethyl acetate extract enzymatic hydrolysate (IC₅₀ = 41.82 μg/mL) was demonstated. The results presented in this work suggested that hemicellulase has promising and attractive properties for industrial production of HT, and indicated that HT might be a valuable biological component for use in pharmaceutical products and functional foods. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 714 KiB

Open AccessArticle

Facile Access to Unnatural Dipeptide-Alcohols Based on cis-2,5-Disubstituted Pyrrolidines

by Yan-Yan Jia^1,†, Xiao-Ye Li^2,†, Ping-An Wang^2,* and Ai-Dong Wen^1,*

¹ Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Changle West Road 15, Xi'an 710032, China

² Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, China

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2922-2930; https://doi.org/10.3390/molecules20022922 - 11 Feb 2015

Viewed by 6218

Abstract

Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(−)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, ¹H- and ¹³C-NMR spectroscopy. These unnatural dipeptide-alcohols [...] Read more.

Well-defined unnatural dipeptide-alcohols based on a cis-2,5-disubstitued pyrrolidine backbone were synthesized from commercially available starting materials meso-diethyl-2,5-dibromoadipate, (S)-(−)-1-phenylethylamine, and phenylalaninol. The structures of these unnatural dipeptide-alcohols are supported by HRMS, ¹H- and ¹³C-NMR spectroscopy. These unnatural dipeptide-alcohols can act as building blocks for peptidomimetics. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Conjugated and Non Conjugated Small Molecules)

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18 pages, 3358 KiB

Open AccessArticle

Inhibitory Effects of Neochamaejasmin B on P-Glycoprotein in MDCK-hMDR1 Cells and Molecular Docking of NCB Binding in P-Glycoprotein

by Lanying Pan^1,2, Haihong Hu¹, Xiangjun Wang², Lushan Yu¹, Huidi Jiang¹, Jianzhong Chen¹, Yan Lou^1,3,* and Su Zeng^1,*

¹ Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

² Laboratory of Natural Medicine, School of Forestry and Bio-technology, Zhejiang A&F University, Lin'an 311300, China

³ The First Affiliated hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310000, China

Molecules 2015, 20(2), 2931-2948; https://doi.org/10.3390/molecules20022931 - 11 Feb 2015

Cited by 24 | Viewed by 8202

Abstract

Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed [...] Read more.

Stellera chamaejasme L. (Thymelaeaceae) is widely distributed in Mongolia, Tibet and the northern parts of China. Its roots are commonly used as “Langdu”, which is embodied in the Pharmacopoeia of the P.R. China (2010) as a toxic Traditional Chinese Medicine. It is claimed to have antivirus, antitumor and antibacterial properties in China and other Asian countries. Studies were carried out to characterize the inhibition of neochamaejasmin B (NCB) on P-glycoprotein (P-gp, ABCB1, MDR1). Rhodamine-123 (R-123) transport and accumulation studies were performed in MDCK-hMDR1 cells. ABCB1 (MDR1) mRNA gene expression and P-gp protein expression were analyzed. Binding selectivity studies based on molecular docking were explored. R-123 transport and accumulation studies in MDCK-hMDR1 cells indicated that NCB inhibited the P-gp-mediated efflux in a concentration-dependent manner. RT-PCR and Western blot demonstrated that the P-gp expression was suppressed by NCB. To investigate the inhibition type of NCB on P-gp, K_i and K_i’ values were determined by double-reciprocal plots in R-123 accumulation studies. Since K_i was greater than K_i’, the inhibition of NCB on P-gp was likely a mixed type of competitive and non-competitive inhibition. The results were confirmed by molecular docking in our current work. The docking data indicated that NCB had higher affinity to P-gp than to Lig1 ((S)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one). Full article

(This article belongs to the Section Natural Products Chemistry)

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24 pages, 1169 KiB

Open AccessArticle

Acid Catalyzed Alcoholysis of Sulfinamides: Unusual Stereochemistry, Kinetics and a Question of Mechanism Involving Sulfurane Intermediates and Their Pseudorotation

by Bogdan Bujnicki, Józef Drabowicz

and Marian Mikołajczyk^*

Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland

Molecules 2015, 20(2), 2949-2972; https://doi.org/10.3390/molecules20022949 - 11 Feb 2015

Cited by 12 | Viewed by 9426

Abstract

The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. [...] Read more.

The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations. Full article

(This article belongs to the Special Issue Dynamic Stereochemistry)

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28 pages, 811 KiB

Open AccessReview

Indole Alkaloids from Catharanthus roseus: Bioproduction and Their Effect on Human Health

by Lorena Almagro^†, Francisco Fernández-Pérez^† and Maria Angeles Pedreño^*

¹ Department of Plant Biology, Faculty of Biology, University of Murcia, Murcia 30100, Spain

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 2973-3000; https://doi.org/10.3390/molecules20022973 - 12 Feb 2015

Cited by 219 | Viewed by 18504

Abstract

Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of [...] Read more.

Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of this plant is based on its enormous pharmaceutical interest, producing more than 130 TIAs, some of which exhibit strong pharmacological activities. The most striking biological activity investigated has been the antitumour effect of dimeric alkaloids such as anhydrovinblastine, vinblastine and vincristine which are already in pre-, clinical or in use. The great pharmacological importance of these indole alkaloids, contrasts with the small amounts of them found in this plant, making their extraction a very expensive process. To overcome this problem, researches have looked for alternative sources and strategies to produce them in higher amounts. In this sense, intensive research on the biosynthesis of TIAs and the regulation of their pathways has been developed with the aim to increase by biotechnological approaches, the production of these high added value compounds. This review is focused on the different strategies which improve TIA production, and in the analysis of the beneficial effects that these compounds exert on human health. Full article

(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)

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19 pages, 1075 KiB

Open AccessArticle

Structural Analysis of Metabolites of Asiatic Acid and Its Analogue Madecassic Acid in Zebrafish Using LC/IT-MSⁿ

by Binbin Xia, Lu Bai, Xiaorong Li, Jie Xiong, Pinxiang Xu and Ming Xue^*

Beijing Laboratory for Biomedical Detection Technology and Instrument, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Molecules 2015, 20(2), 3001-3019; https://doi.org/10.3390/molecules20023001 - 12 Feb 2015

Cited by 34 | Viewed by 11502

Abstract

Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess [...] Read more.

Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess many pharmacological effects. This study is to probe the metabolic capability of zebrafish via investigation of the drug metabolism of AA and MA in zebrafish, using a sensitive LC/IT-MSⁿ method. In addition, the main fragmentation pathways of AA and MA were reported for the first time. Nineteen metabolites of AA and MA were firstly identified after zebrafish was exposed to the drug, which all were the phase I metabolites and mainly formed from hydroxylation, dehydrogenation, hydroxylation and dehydrogenation, dihydroxylation and dehydrogenation, and dehydroxylation reaction. The results indicated that zebrafish possessed strong metabolic capacity, and the metabolites of AA and MA were formed via similar metabolic pathways and well matched with the known metabolic rules in vivo and in vitro, which supports the widely use of this system in drug metabolism research. This investigation would also contribute to the novel information on the structural elucidation, in vivo metabolites and metabolic mechanism of pentacyclic triterpenoids. Full article

(This article belongs to the Section Metabolites)

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7 pages, 681 KiB

Open AccessReview

Curcumin and Omega-3 Fatty Acids Enhance NK Cell-Induced Apoptosis of Pancreatic Cancer Cells but Curcumin Inhibits Interferon-γ Production: Benefits of Omega-3 with Curcumin against Cancer

by Milan Fiala

Department of Surgery, School of Medicine, University of California, Los Angeles, CA 90095, USA

Molecules 2015, 20(2), 3020-3026; https://doi.org/10.3390/molecules20023020 - 12 Feb 2015

Cited by 53 | Viewed by 15952

Abstract

STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB [...] Read more.

STAT-3 and STAT-1 signaling have opposite effects in oncogenesis with STAT-3 acting as an oncogene and STAT-1 exerting anti-oncogenic activities through interferon-γ and interferon-α. The cytokine IL-6 promotes oncogenesis by stimulation of NFκB and STAT-3 signaling. Curcuminoids have bi-functional effects by blocking NFκB anti-apoptotic signaling but also blocking anti-oncogenic STAT-1 signaling and interferon-γ production. In our recent study (unpublished work [1]) in pancreatic cancer cell cultures, curcuminoids enhanced cancer cell apoptosis both directly and by potentiating natural killer (NK) cell cytotoxic function. The cytotoxic effects of curcuminoids were increased by incubation of cancer cells and NK cells in an emulsion with omega-3 fatty acids and antioxidants (Smartfish), which enhanced cancer cell apoptosis and protected NK cells against degradation. However, as also shown by others, curcuminoids blocked interferon-γ production by NK cells. The combined use of curcuminoids and omega-3 in cancer immunotherapy will require deeper understanding of their in vivo interactions with the immune system. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

23 pages, 4198 KiB

Open AccessReview

Inhibitors of the AAA+ Chaperone p97

by Eli Chapman^*, Nick Maksim, Fabian De la Cruz and James J. La Clair

Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721-0207, USA

Molecules 2015, 20(2), 3027-3049; https://doi.org/10.3390/molecules20023027 - 12 Feb 2015

Cited by 79 | Viewed by 12619 | Correction

Abstract

It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA) more than 10 years ago to treat refractory [...] Read more.

It is remarkable that a pathway as ubiquitous as protein quality control can be targeted to treat cancer. Bortezomib, an inhibitor of the proteasome, was first approved by the US Food and Drug Administration (FDA) more than 10 years ago to treat refractory myeloma and later extended to lymphoma. Its use has increased the survival rate of myeloma patients by as much as three years. This success was followed with the recent accelerated approval of the natural product derived proteasome inhibitor carfilzomib (Kyprolis^®), which is used to treat patients with bortezomib-resistant multiple myeloma. The success of these two drugs has validated protein quality control as a viable target to fight select cancers, but begs the question why are proteasome inhibitors limited to lymphoma and myeloma? More recently, these limitations have encouraged the search for additional targets within the protein quality control system that might offer heightened cancer cell specificity, enhanced clinical utility, a lower rate of resistance, reduced toxicity, and mitigated side effects. One promising target is p97, an ATPase associated with various cellular activities (AAA+) chaperone. p97 figures prominently in protein quality control as well as serving a variety of other cellular functions associated with cancer. More than a decade ago, it was determined that up-regulation of p97 in many forms of cancer correlates with a poor clinical outcome. Since these initial discoveries, a mechanistic explanation for this observation has been partially illuminated, but details are lacking. Understandably, given this clinical correlation, myriad roles within the cell, and its importance in protein quality control, p97 has emerged as a potential therapeutic target. This review provides an overview of efforts towards the discovery of small molecule inhibitors of p97, offering a synopsis of efforts that parallel the excellent reviews that currently exist on p97 structure, function, and physiology. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 859 KiB

Open AccessArticle

New Pregnane Glycosides from Gymnema sylvestre

by Rui Xu, Yu Yang, Yang Zhang, Fengxia Ren, Jinlong Xu, Nengjiang Yu^* and Yimin Zhao^*

Institute of Pharmacology and Toxicology, Academy for Military Medical Science, 27 Taiping Road, Haidian District, Beijing 100850, China

Molecules 2015, 20(2), 3050-3066; https://doi.org/10.3390/molecules20023050 - 12 Feb 2015

Cited by 17 | Viewed by 6989

Abstract

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined [...] Read more.

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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22 pages, 1404 KiB

Open AccessArticle

Novel Orally Active Analgesic and Anti-Inflammatory Cyclohexyl-N-Acylhydrazone Derivatives

by Tiago Fernandes Da Silva^1,2, Walfrido Bispo Júnior³, Magna Suzana Alexandre-Moreira³, Fanny Nascimento Costa^4,5, Carlos Eduardo da Silva Monteiro⁶, Fabio Furlan Ferreira⁴

, Regina Cely Rodrigues Barroso⁵, François Noël⁶, Roberto Takashi Sudo⁶, Gisele Zapata-Sudo⁶, Lídia Moreira Lima^1,2,6,* and Eliezer J. Barreiro^1,2,6,*

¹ Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio®), Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos (INCT-INOFAR), Universidade Federal do Rio de Janeiro, CCS, Cidade Universitária, P.O. Box 68024, Rio de Janeiro-RJ 21941-971, Brazil

² Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro-RJ 21941-909, Brazil

³ LaFI—Laboratório de Farmacologia e Imunidade, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió-AL 57072-900, Brazil

⁴ Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC) Av. dos Estados 5001, Santo André-SP 09210-580, Brazil

⁵ Physics Institute, UERJ, Rio de Janeiro-RJ 20550-900, Brazil

⁶ Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro-RJ 21941-902, Brazil

Molecules 2015, 20(2), 3067-3088; https://doi.org/10.3390/molecules20023067 - 12 Feb 2015

Cited by 44 | Viewed by 8582

Abstract

The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of [...] Read more.

The N-acylhydrazone (NAH) moiety is considered a privileged structure, being present in many compounds with diverse pharmacological activities. Among the activities attributed to NAH derivatives anti-inflammatory and analgesic ones are recurrent. As part of a research program aiming at the design of new analgesic and anti-inflammatory lead-candidates, a series of cyclohexyl-N-acylhydrazones 10–26 were structurally designed from molecular modification on the prototype LASSBio-294, representing a new class of cycloalkyl analogues. Compounds 10–26 and their conformationally restricted analogue 9 were synthetized and evaluated as analgesic and anti-inflammatory agents in classical pharmacologic protocols. The cyclohexyl-N-acylhydrazones 10–26 and the cyclohexenyl analogue 9 showed great anti-inflammatory and/or analgesic activities, but compound 13 stood out as a new prototype to treat acute and chronic painful states due to its important analgesic activity in a neuropathic pain model. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 1466 KiB

Open AccessArticle

Selective C–C Coupling Reaction of Dimethylphenol to Tetramethyldiphenoquinone Using Molecular Oxygen Catalyzed by Cu Complexes Immobilized in Nanospaces of Structurally-Ordered Materials

by Zen Maeno¹, Takato Mitsudome¹, Tomoo Mizugaki¹, Koichiro Jitsukawa¹ and Kiyotomi Kaneda^1,2,*

¹ Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, 1-3, Machikaneyama, Toyonaka, Osaka 560-8531, Japan

² Research Center for Solar Energy Chemistry, Osaka University, 1-3, Machikaneyama, Toyonaka, Osaka 560-8531, Japan

Molecules 2015, 20(2), 3089-3106; https://doi.org/10.3390/molecules20023089 - 12 Feb 2015

Cited by 11 | Viewed by 10808

Abstract

Two high-performance Cu catalysts were successfully developed by immobilization of Cu ions in the nanospaces of poly(propylene imine) (PPI) dendrimer and magadiite for the selective C–C coupling of 2,6-dimethylphenol (DMP) to 3,3',5,5'-tetramethyldiphenoquinone (DPQ) with O₂ as a green oxidant. The PPI dendrimer [...] Read more.

Two high-performance Cu catalysts were successfully developed by immobilization of Cu ions in the nanospaces of poly(propylene imine) (PPI) dendrimer and magadiite for the selective C–C coupling of 2,6-dimethylphenol (DMP) to 3,3',5,5'-tetramethyldiphenoquinone (DPQ) with O₂ as a green oxidant. The PPI dendrimer encapsulated Cu ions in the internal nanovoids to form adjacent Cu species, which exhibited significantly high catalytic activity for the regioselective coupling reaction of DMP compared to previously reported enzyme and metal complex catalysts. The magadiite-immobilized Cu complex acted as a selective heterogeneous catalyst for the oxidative C–C coupling of DMP to DPQ. This heterogeneous catalyst was recoverable from the reaction mixture by simple filtration, reusable without loss of efficiency, and applicable to a continuous flow reactor system. Detailed characterization using ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR), electronic spin resonance (ESR), and X-ray absorption fine structure (XAFS) spectroscopies and the reaction mechanism investigation revealed that the high catalytic performances of these Cu catalysts were ascribed to the adjacent Cu species generated within the nanospaces of the PPI dendrimer and magadiite. Full article

(This article belongs to the Special Issue Frontier in Green Chemistry Approaches)

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22 pages, 830 KiB

Open AccessArticle

Urine and Serum Metabolite Profiling of Rats Fed a High-Fat Diet and the Anti-Obesity Effects of Caffeine Consumption

by Hyang Yeon Kim¹, Mee Youn Lee¹, Hye Min Park¹, Yoo Kyoung Park²

, Jong Cheol Shon³, Kwang-Hyeon Liu³

and Choong Hwan Lee^1,*

¹ Department of Bioscience and Biotechnology, Kon-Kuk University, Seoul 143-701, Korea

² Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do 446-791, Korea

³ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea

Molecules 2015, 20(2), 3107-3128; https://doi.org/10.3390/molecules20023107 - 13 Feb 2015

Cited by 37 | Viewed by 10846

Abstract

In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without [...] Read more.

In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling. Full article

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

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17 pages, 3316 KiB

Open AccessArticle

Potential Quality Evaluation Method for Radix Astragali Based on Sweetness Indicators

by Ke Li¹, Fanrong Gao^1,2, Zhenyu Li¹, Xuemei Qin^1,*, Haifeng Sun², Jie Xing^1,2, Lizeng Zhang^1,2 and Guanhua Du^1,3

¹ Modern Research Center for Traditional Chinese Medicine, Shanxi University, No.92, Wucheng Road, Taiyuan 030006, China

² College of Chemistry and Chemical Engineering, Shanxi University, No.92, Wucheng Road, Taiyuan 030006, China

³ Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China

Molecules 2015, 20(2), 3129-3145; https://doi.org/10.3390/molecules20023129 - 13 Feb 2015

Cited by 7 | Viewed by 6330

Abstract

Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, [...] Read more.

Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, nor a scientific investigation of the reliability of this indicator has been conducted to date. In this study, seven kinds of sweetness components were identified in RA and a quality evaluation method based on these components was established and used to characterize the quality of 48 RA samples. The sweetness evaluation method of RA was first built based on the sweetness components, and a comprehensive evaluation index commonly used in quality control of RA was also derived, which was based on the contents of four indicators (astragaloside IV, calycosin glucoside, polysaccharides and extracts). After evaluating the correlation of these indexes the results showed that the level of sweetness exhibited a strong positive correlation with the proposed comprehensive index. Our results indicate that sweetness is one of the most important quality attributes of RA and thus provide a scientific basis for the utility of the sweetness indicator in quality assessment of this Chinese herb. Full article

(This article belongs to the Section Natural Products Chemistry)

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24 pages, 2646 KiB

Open AccessArticle

Spectroscopic (FT-IR, FT-Raman, ¹H- and ¹³C-NMR), Theoretical and Microbiological Study of trans o-Coumaric Acid and Alkali Metal o-Coumarates

by Małgorzata Kowczyk-Sadowy¹, Renata Świsłocka¹, Hanna Lewandowska²

, Jolanta Piekut¹ and Włodzimierz Lewandowski^1,*

¹ Division of Chemistry, Bialystok University of Technology, Wiejska 45E, Bialystok 15-351, Poland

² Institute of Nuclear Chemistry and Technology, 16 Dorodna St., Warsaw 03-195, Poland

Molecules 2015, 20(2), 3146-3169; https://doi.org/10.3390/molecules20023146 - 13 Feb 2015

Cited by 57 | Viewed by 11786

Abstract

This work is a continuation of research on a correlation between the molecular structure and electronic charge distribution of phenolic compounds and their biological activity. The influence of lithium, sodium, potassium, rubidium and cesium cations on the electronic system of trans o-coumaric [...] Read more.

This work is a continuation of research on a correlation between the molecular structure and electronic charge distribution of phenolic compounds and their biological activity. The influence of lithium, sodium, potassium, rubidium and cesium cations on the electronic system of trans o-coumaric (2-hydroxy-cinnamic) acid was studied. We investigated the relationship between the molecular structure of the tested compounds and their antimicrobial activity. Complementary molecular spectroscopic techniques such as infrared (FT-IR), Raman (FT-Raman), ultraviolet-visible (UV-VIS) and nuclear magnetic resonance (¹H- and ¹³C-NMR) were applied. Structures of the molecules were optimized and their structural characteristics were calculated by the density functional theory (DFT) using the B3LYP method with 6-311++G** as a basis set. Geometric and magnetic aromaticity indices, atomic charges, dipole moments and energies were also calculated. Theoretical parameters were compared to the experimental characteristics of investigated compounds. Correlations between certain vibrational bands and some metal parameters, such as electronegativity, ionization energy, atomic and ionic radius, were found. The microbial activity of studied compounds was tested against Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Proteus vulgaris and Candida albicans. Full article

(This article belongs to the Section Molecular Diversity)

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20 pages, 680 KiB

Open AccessArticle

Synthesis and Antimicrobial Activity of N-Substituted-β-amino Acid Derivatives Containing 2-Hydroxyphenyl, Benzo[b]phenoxazine and Quinoxaline Moieties

by Kristina Mickevičienė¹, Rūta Baranauskaitė², Kristina Kantminienė^1,*, Maryna Stasevych³, Olena Komarovska-Porokhnyavets³ and Volodymyr Novikov³

¹ Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Kaunas 50254, Lithuania

² Department of Organic Chemistry, Kaunas University of Technology, Kaunas 50254, Lithuania

³ Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Politechnic National University, Lviv-13 79013, Ukraine

Molecules 2015, 20(2), 3170-3189; https://doi.org/10.3390/molecules20023170 - 13 Feb 2015

Cited by 33 | Viewed by 8811

Abstract

3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity [...] Read more.

3-[(2-Hydroxyphenyl)amino]butanoic and 3-[(2-hydroxy-5-methyl(chloro)phenyl)amino]butanoic acids were converted to a series of derivatives containing hydrazide, pyrrole and chloroquinoxaline moieties. The corresponding benzo[b]phenoxazine derivatives were synthesized by the reaction of the obtained compounds with 2,3-dichloro-1,4-naphthoquinone. Five of the synthesized compounds exhibited good antimicrobial activity against Staphylococcus aureus and Mycobacterium luteum, whereas three compounds showed significant antifungal activity against Candida tenuis and Aspergillus niger. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1053 KiB

Open AccessReview

Development of Bioorthogonal Reactions and Their Applications in Bioconjugation

by Mengmeng Zheng, Li Zheng, Peiyuan Zhang, Jinbo Li^* and Yan Zhang^*

Institute of Chemistry & BioMedical Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China

Molecules 2015, 20(2), 3190-3205; https://doi.org/10.3390/molecules20023190 - 16 Feb 2015

Cited by 44 | Viewed by 14592

Abstract

Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and [...] Read more.

Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and selective ligation under bio-compatible conditions have found diverse applications in the development of new bioconjugation strategies. The development of new bioorthogonal reactions in the past decade has been summarized with comments on their potentials as bioconjugation method in the construction of various biological probes for investigating their target biomolecules. For the applications of bioorthogonal reactions in the site-selective biomolecule conjugation, examples have been presented on the bioconjugation of protein, glycan, nucleic acids and lipids. Full article

(This article belongs to the Special Issue Bioconjugations)

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15 pages, 1667 KiB

Open AccessArticle

Inhibitory Effect of Triterpenoids from Dillenia serrata (Dilleniaceae) on Prostaglandin E₂ Production and Quantitative HPLC Analysis of Its Koetjapic Acid and Betulinic Acid Contents

by Juriyati Jalil^1,*, Carla W. Sabandar¹, Norizan Ahmat², Jamia A. Jamal¹, Ibrahim Jantan¹, Nor-Ashila Aladdin¹, Kartiniwati Muhammad¹, Fhataheya Buang¹, Hazni Falina Mohamad¹ and Idin Sahidin³

¹ Drug Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia

² Faculty of Applied Sciences, Universiti Teknologi Mara, Shah Alam 40450, Malaysia

³ Laboratory of Natural Products Chemistry, Faculty of Pharmacy, Halu Oleo University, Kendari 93232, Indonesia

Molecules 2015, 20(2), 3206-3220; https://doi.org/10.3390/molecules20023206 - 16 Feb 2015

Cited by 29 | Viewed by 8246

Abstract

The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E₂ (PGE₂) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated [...] Read more.

The crude methanol extracts and fractions of the root and stem barks of Dillenia serrata Thunb. showed 64% to 73% inhibition on the production of prostaglandin E₂ (PGE₂) in lipopolysaccharide-induced human whole blood using a radioimmunoassay technique. Three triterpenoids isolated from the root bark of the plant, koetjapic (1), 3-oxoolean-12-en-30-oic (2), and betulinic (3) acids, exhibited significant concentration-dependent inhibitory effects on PGE₂ production with IC₅₀ values of 1.05, 1.54, and 2.59 μM, respectively, as compared with the positive control, indomethacin (IC₅₀ = 0.45 μM). Quantification of compounds 1 and 3 in the methanol extracts and fractions were carried out by using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method. The ethyl acetate fraction of the stem bark showed the highest content of both compound 1 (15.1%) and compound 3 (52.8%). The strong inhibition of the extracts and fractions on cyclooxygenase-2 (COX-2) enzymatic activity was due to the presence of their major constituents, especially koetjapic and betulinic acids. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 768 KiB

Open AccessArticle

Isolation and Characterisation of in Vitro and Cellular Free Radical Scavenging Peptides from Corn Peptide Fractions

by Liying Wang¹, Long Ding¹, Ying Wang^1,2, Yan Zhang¹ and Jingbo Liu^1,*

¹ Laboratory of Nutrition and Functional Food, Jilin University, Changchun 130062, China

² College of Biological and Agricultural Engineering, Jilin University, Changchun 130062, China

Molecules 2015, 20(2), 3221-3237; https://doi.org/10.3390/molecules20023221 - 16 Feb 2015

Cited by 63 | Viewed by 9042

Abstract

Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) [...] Read more.

Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) were investigated. Results indicated that CPF1 (molecular weight less than 1 kDa) and CPF2 (molecular weight between 1 and 3 kDa) exhibited good hydroxyl radical, superoxide anion radical and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) diammonium salt (ABTS) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Meanwhile, the in vitro radical scavenging activity of CPF1 was slightly higher than that of CPF2. Both CPF1 and CPF2 also exhibited significant cytoprotective effects and intracellular reactive oxygen species scavenging activity in Caco-2 cells exposed to hydrogen peroxide (H₂O₂). The amino acid composition analysis revealed that the CPF were rich in hydrophobic amino acids, which comprised of more than 45% of total amino acids. An antioxidant peptide sequence of Tyr-Phe-Cys-Leu-Thr (YFCLT) was identified from CPF1 using matrix-assisted laser desorption/ionization time-of-flight/time-of-ﬂight mass spectrometry (MALDI TOF/TOF MS). The YFCLT exhibited excellent ABTS radical scavenging activity with a 50% effective concentration (EC₅₀) value of 37.63 µM, which was much lower than that of Trolox. In conclusion, corn gluten meal might be a good source to prepare antioxidant peptides. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

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17 pages, 1208 KiB

Open AccessCommunication

Toxicity of Amorphigenin from the Seeds of Amorpha fruticosa against the Larvae of Culex pipiens pallens (Diptera: Culicidae)

by Yaping Liang¹, Xiuwei Li^1,*, Zumin Gu¹, Peiwen Qin¹ and Mingshan Ji^1,2,*

¹ Department of Pesticide Science, College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, China

² Biopesticide Engineering Research Center of Liaoning Province, Shenyang 110866, China

Molecules 2015, 20(2), 3238-3254; https://doi.org/10.3390/molecules20023238 - 16 Feb 2015

Cited by 18 | Viewed by 7554

Abstract

The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, [...] Read more.

The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, the ethanol one exhibited the highest larvicidal activity (LC₅₀ = 22.69 mg/L). Amorphigenin (8'-hydroxyrotenone), a rotenoid compound which exhibits a strong larvicidal activity with LC₅₀ and LC₉₀values of 4.29 and 11.27 mg/L, respectively, was isolated from the ethanol extract by column chromatograpy. Its structure was elucidated by ¹H-NMR, UV and IR spectral data. Furthermore, investigation of amorphigenin’s effects on mitochondrial complex I activity and protein synthesis in C. pipiens pallens larvae reveals that amorphigenin decreases mitochondrial complex I activities to 65.73% at 10.45 μmol/L, compared to the control, when NADH were used as the substrate. Meanwhile, amorphigenin at 10.45 μmol/L also caused a 1.98-fold decrease in protein content, compared to the control larvae treated with acetone only. Full article

(This article belongs to the Section Natural Products Chemistry)

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26 pages, 911 KiB

Open AccessArticle

Design, Synthesis, and Cytotoxicity of Perbutyrylated Glycosides of 4β-Triazolopodophyllotoxin Derivatives

by Cheng-Ting Zi^1,2, Zhen-Hua Liu², Gen-Tao Li², Yan Li², Jun Zhou², Zhong-Tao Ding^1,*, Jiang-Miao Hu^2,* and Zi-Hua Jiang^3,*

¹ Key Laboratory of Medicinal Chemistry for Nature Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China

² State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

³ Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, ON P7B 5E1, Canada

Molecules 2015, 20(2), 3255-3280; https://doi.org/10.3390/molecules20023255 - 16 Feb 2015

Cited by 18 | Viewed by 6585

Abstract

A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some [...] Read more.

A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC₅₀ values ranging from 0.49 to 6.70 μM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+)-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 754 KiB

Open AccessArticle

Three New Lanostanoids from the Mushroom Ganoderma tropicum

by Shuang-Shuang Zhang¹, Yu-Guang Wang², Qing-Yun Ma², Sheng-Zhuo Huang², Li-Li Hu², Hao-Fu Dai², Zhi-Fang Yu^1,* and You-Xing Zhao^2,*

¹ College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China

² Key Laboratory of Biology and Genetic Resources of Tropical Crops, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China

Molecules 2015, 20(2), 3281-3289; https://doi.org/10.3390/molecules20023281 - 16 Feb 2015

Cited by 24 | Viewed by 7069

Abstract

Three new lanostanoid triterpenes—ganotropic acid (1), 3β,7β,15α,24-tetra- hydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2) and 3β,7β,15α,28-tetrahydroxy-11,23- dioxo-lanost-8,16-dien-26-oic acid (3)—were isolated from the n-BuOH extract of the fruiting bodies of the mushroom Ganoderma tropicum. Their structures were elucidated by 1D [...] Read more.

Three new lanostanoid triterpenes—ganotropic acid (1), 3β,7β,15α,24-tetra- hydroxy-11,23-dioxo-lanost-8-en-26-oic acid (2) and 3β,7β,15α,28-tetrahydroxy-11,23- dioxo-lanost-8,16-dien-26-oic acid (3)—were isolated from the n-BuOH extract of the fruiting bodies of the mushroom Ganoderma tropicum. Their structures were elucidated by 1D and 2D NMR spectroscopy, as well as HR-EI-MS data. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 977 KiB

Open AccessArticle

Study of Coumarin-Resveratrol Hybrids as Potent Antioxidant Compounds

by Maria J. Matos^1,2,*,†

, Francisco Mura^3,†, Saleta Vazquez-Rodriguez^1,2,†, Fernanda Borges^1,†, Lourdes Santana^2,†, Eugenio Uriarte^2,† and Claudio Olea-Azar^3,*,†

¹ CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, Portugal

² Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain

³ Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233 Santiago, Chile

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 3290-3308; https://doi.org/10.3390/molecules20023290 - 16 Feb 2015

Cited by 45 | Viewed by 9818

Abstract

In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 5–8, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it [...] Read more.

In the present work we synthesized a selected series of hydroxylated 3-phenylcoumarins 5–8, with the aim of evaluating in detail their antioxidant properties. From an in depth study of the antioxidant capacity data (ORAC-FL, ESR, CV and ROS inhibition) it was concluded that these derivatives are very good antioxidants, with very interesting profiles in all the performed assays. The study of the effect of the number and position of the hydroxyl groups on the antioxidant activity was the principal aim of this study. In particular, 7-hydroxy-3-(3'-hydroxy)phenylcoumarin (8) proved to be the most active and effective antioxidant of the selected series in four of the performed assays (ORAC-FL = 11.8, capacity of scavenging hydroxyl radicals = 54%, Trolox index = 2.33 and AI₃₀ index = 0.18). However, the presence of two hydroxyl groups on this molecule did not increase greatly the activity profile. Theoretical evaluation of ADME properties of all the derivatives was also carried out. All the compounds can act as potential candidates for preventing or minimizing the free radical overproduction in oxidative-stress related diseases. These preliminary findings encourage us to perform a future structural optimization of this family of compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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26 pages, 731 KiB

Open AccessReview

Prevention of Protein Glycation by Natural Compounds

by Izabela Sadowska-Bartosz^1,* and Grzegorz Bartosz^1,2

¹ Department of Biochemistry and Cell Biology, University of Rzeszow, Zelwerowicza St. 4, PL 35-601 Rzeszow, Poland

² Department of Molecular Biophysics, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland

Molecules 2015, 20(2), 3309-3334; https://doi.org/10.3390/molecules20023309 - 16 Feb 2015

Cited by 140 | Viewed by 14385

Abstract

Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, [...] Read more.

Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, especially polyphenols and other natural antioxidants. Extrapolation of results of in vitro studies on the in vivo situation is not straightforward due to differences in the conditions and mechanism of glycation, and bioavailability problems. Nevertheless, available data allow to postulate that enrichment of diet in natural anti-glycating agents may attenuate glycation and, in consequence, ageing. Full article

(This article belongs to the Special Issue Natural Antioxidants and Ageing)

19 pages, 1047 KiB

Open AccessArticle

Lactones with Methylcyclohexane Systems Obtained by Chemical and Microbiological Methods and Their Antimicrobial Activity

by Małgorzata Grabarczyk^1,*, Katarzyna Wińska¹, Wanda Mączka¹, Anna K. Żołnierczyk¹, Barbara Żarowska²

and Mirosław Anioł¹

¹ Department of Chemistry, University of Environmental and Life Sciences, Norwida 25, Wrocław 50-375, Poland

² Department of Biotechnology and Food Microbiology, University of Environmental and Life Sciences, Chełmońskiego 37/41, Wrocław 51-630, Poland

Molecules 2015, 20(2), 3335-3353; https://doi.org/10.3390/molecules20023335 - 16 Feb 2015

Cited by 18 | Viewed by 6363

Abstract

Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones), each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl) acetic acid or (6-methylcyclohex-2-en-1-yl) acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea) were tested on [...] Read more.

Eight new lactones (δ-chloro-, δ-bromo- and δ-iodo-γ-lactones), each with a methylcyclohexane ring, were obtained by chemical means from (4-methylcyclohex-2-en-1-yl) acetic acid or (6-methylcyclohex-2-en-1-yl) acetic acid. Whole cells of ten fungal strains (Fusarium species, Syncephalastrum racemosum and Botrytis cinerea) were tested on their ability to convert these lactones into other products. Some of the tested fungal strains transformed chloro-, bromo- and iodolactone with a methyl group at C-5 into 2-hydroxy-5-methyl-9-oxabicyclo[4.3.0]nonan-8-one during hydrolytic dehalogenation. When the same lactones had the methyl group at C-3, no structural modifications of halolactones were observed. In most cases, the optical purity of the product was low or medium, with the highest rate for chlorolactone (45.4%) and iodolactone (45.2% and 47.6%). All of the obtained compounds were tested with reference to their smell. Seven halolactones and the hydroxylactone obtained via biotransformation of halolactones with 5-methylcyclohexane ring were examined for their antimicrobial activity. These compounds were capable of inhibiting growth of some bacteria, yeasts and fungi. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 2646 KiB

Open AccessArticle

Investigation of Structural Mimetics of Natural Phosphate Ion Binding Motifs

by Evgeny A. Kataev^*,† and Tatiana A. Shumilova^†

¹ Institute of Chemistry, Faculty of Natural Sciences, Technische Universität Chemnitz, 09107 Chemnitz, Germany

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 3354-3370; https://doi.org/10.3390/molecules20023354 - 16 Feb 2015

Cited by 8 | Viewed by 7637

Abstract

Phosphates are ubiquitous in biology and nearly half of all proteins interact with their partners by means of recognition of phosphate residues. Therefore, a better understanding of the phosphate ion binding by peptidic structures is highly desirable. Two new receptors have been designed [...] Read more.

Phosphates are ubiquitous in biology and nearly half of all proteins interact with their partners by means of recognition of phosphate residues. Therefore, a better understanding of the phosphate ion binding by peptidic structures is highly desirable. Two new receptors have been designed and synthesized and their anion binding properties in an acetonitrile solution have been determined. The structure of hosts mimics a part of the kinase active site that is responsible for the recognition of the phosphate residue. New hosts contain additional free amino groups with the aim to facilitate coordination of protonated anions, such as dihydrogen phosphate. According to spectrophotometric measurements, stepwise 1:1 and 1:2 binding modes have been observed for both receptors in the presence of acetate, hydrogen sulfate and dihydrogen phosphate. Compared with the acyclic receptor, the macrocyclic receptor has demonstrated a remarkably enhanced selectivity for dihydrogen phosphate over other anions. Fluorometric measurements have revealed different responses of the acyclic and macrocyclic receptors towards anions. However, in both cases, a 5–8 nm hypsochromic shift of fluorescence maximum has been observed upon interaction of acetate and dihydrogen phosphate with receptors. Full article

(This article belongs to the Special Issue Host-Guest Chemistry)

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18 pages, 3775 KiB

Open AccessArticle

A Density Functional Tight Binding Study of Acetic Acid Adsorption on Crystalline and Amorphous Surfaces of Titania

by Sergei Manzhos^1,*, Giacomo Giorgi^2,3 and Koichi Yamashita^2,3

¹ Department of Mechanical Engineering, National University of Singapore, Block EA #07-08, 9 Engineering Drive 1, Singapore 117576, Singapore

² Department of Chemical System Engineering, School of Engineering, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan

³ CREST-JST, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan

Molecules 2015, 20(2), 3371-3388; https://doi.org/10.3390/molecules20023371 - 17 Feb 2015

Cited by 44 | Viewed by 10708

Abstract

We present a comparative density functional tight binding study of an organic molecule attachment to TiO₂ via a carboxylic group, with the example of acetic acid. For the first time, binding to low-energy surfaces of crystalline anatase (101), rutile (110) and (B)-TiO [...] Read more.

We present a comparative density functional tight binding study of an organic molecule attachment to TiO₂ via a carboxylic group, with the example of acetic acid. For the first time, binding to low-energy surfaces of crystalline anatase (101), rutile (110) and (B)-TiO₂ (001), as well as to the surface of amorphous (a-) TiO₂ is compared with the same computational setup. On all surfaces, bidentate configurations are identified as providing the strongest adsorption energy, E_ads = −1.93, −2.49 and −1.09 eV for anatase, rutile and (B)-TiO₂, respectively. For monodentate configurations, the strongest E_ads = −1.06, −1.11 and −0.86 eV for anatase, rutile and (B)-TiO₂, respectively. Multiple monodentate and bidentate configurations are identified on a-TiO₂ with a distribution of adsorption energies and with the lowest energy configuration having stronger bonding than that of the crystalline counterparts, with E_ads up to −4.92 eV for bidentate and −1.83 eV for monodentate adsorption. Amorphous TiO₂ can therefore be used to achieve strong anchoring of organic molecules, such as dyes, that bind via a -COOH group. While the presence of the surface leads to a contraction of the band gap vs. the bulk, molecular adsorption caused no appreciable effect on the band structure around the gap in any of the systems. Full article

(This article belongs to the Special Issue Molecular Engineering for Electrochemical Power Sources)

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17 pages, 1837 KiB

Open AccessArticle

Investigation of Chemomarkers of Astragali Radix of Different Ages and Geographical Origin by NMR Profiling

by Lu Zheng¹, Mei Wang^2,3, Emmanuel Ibarra-Estrada², Changsheng Wu², Erica Georgina Wilson², Robert Verpoorte²

, Petrus Gerardus Leonardus Klinkhamer⁴ and Young Hae Choi^2,*

¹ Shanghai Haini Pharmaceutical Co. Ltd., Yangtze River Pharmaceutical Group, Shanghai 201318, China

² Natural Products Laboratory, Institute of Biology, Leiden University, Sylviusweg 72, Leiden 2333 BE, The Netherlands

³ Sino-Dutch Centre for preventive and Personalized Medicine, Zernikedreef 9, Leiden 2333 CK, The Netherlands

⁴ Plant Ecology and Phytochemistry, Institute of Biology, Leiden University, Sylviusweg 72, Leiden 2333 BE, The Netherlands

Molecules 2015, 20(2), 3389-3405; https://doi.org/10.3390/molecules20023389 - 17 Feb 2015

Cited by 23 | Viewed by 8286

Abstract

Astragalus roots from Astragalus membranaceus Bunge or Astragalus membranaceus var. mongholicus (Bunge) Hsiao are among the most popular traditional medicinal plants due to their diverse therapeutic uses based on their tonic, antinephritic, immunostimulant, hepatoprotectant, diuretic, antidiabetic, analgesic, expectorant and sedative properties. Currently, the [...] Read more.

Astragalus roots from Astragalus membranaceus Bunge or Astragalus membranaceus var. mongholicus (Bunge) Hsiao are among the most popular traditional medicinal plants due to their diverse therapeutic uses based on their tonic, antinephritic, immunostimulant, hepatoprotectant, diuretic, antidiabetic, analgesic, expectorant and sedative properties. Currently, the herb is produced or cultivated in various sites, including 10 different locations in China with very diverse environmental conditions. These differences affect their metabolic pools and consequently their medicinal properties. The comparative metabolic profiling of plants of different geographical origins or ages could contribute to detect biomarkers for their quality control and thus guarantee the efficacy of the herbal medicines produced with this drug. In this paper nuclear magnetic resonance spectroscopy (NMR)-based metabolomics was applied for to plants of different origins and age for this purpose. The results of this study show that in the set of samples evaluated, age is more discriminating than geographical location. The quantity of individual flavonoids and some primary metabolites contributed most to this age differentiation. On the other hand, based on the analysis of orthogonal partial least square (OPLS) modeling, the marker metabolites for the geographical origin were saponins and isoflavonoids. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 3405 KiB

Open AccessArticle

Anti-Proliferative Effect and Induction of Apoptosis in Androgen-Independent Human Prostate Cancer Cells by 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one

by Kamini Citalingam¹, Faridah Abas^2,3,†, Nordin H. Lajis^3,†, Iekhsan Othman^1,*,†

and Rakesh Naidu^1,*

¹ Jeffery Cheah School of Medicine & Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia

² Laboratory of Natural Products, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

³ Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

^† These authors contributed equally to this work.

Molecules 2015, 20(2), 3406-3430; https://doi.org/10.3390/molecules20023406 - 17 Feb 2015

Cited by 24 | Viewed by 8349

Abstract

Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic [...] Read more.

Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC₅₀ values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer. Full article

(This article belongs to the Section Medicinal Chemistry)

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32 pages, 4126 KiB

Open AccessReview

Analysis of Phenolic and Cyclic Compounds in Plants Using Derivatization Techniques in Combination with GC-MS-Based Metabolite Profiling

by Jens Rohloff

Department of Biology, Norwegian University of Science and Technology, Trondheim 7491, Norway

Molecules 2015, 20(2), 3431-3462; https://doi.org/10.3390/molecules20023431 - 17 Feb 2015

Cited by 78 | Viewed by 21057

Abstract

Metabolite profiling has been established as a modern technology platform for the description of complex chemical matrices and compound identification in biological samples. Gas chromatography coupled with mass spectrometry (GC-MS) in particular is a fast and accurate method widely applied in diagnostics, functional [...] Read more.

Metabolite profiling has been established as a modern technology platform for the description of complex chemical matrices and compound identification in biological samples. Gas chromatography coupled with mass spectrometry (GC-MS) in particular is a fast and accurate method widely applied in diagnostics, functional genomics and for screening purposes. Following solvent extraction and derivatization, hundreds of metabolites from different chemical groups can be characterized in one analytical run. Besides sugars, acids, and polyols, diverse phenolic and other cyclic metabolites can be efficiently detected by metabolite profiling. The review describes own results from plant research to exemplify the applicability of GC-MS profiling and concurrent detection and identification of phenolics and other cyclic structures. Full article

(This article belongs to the Section Molecular Diversity)

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16 pages, 1044 KiB

Open AccessReview

Nkrp1 Family, from Lectins to Protein Interacting Molecules

by Daniel Rozbeský^1,2, Ljubina Ivanova¹, Lucie Hernychová^1,3, Valéria Grobárová³, Petr Novák^1,2 and Jan Černý^3,*

¹ Institute of Microbiology, v.v.i., Academy of Sciences of the Czech Republic, Vídeňská 1083, Prague 414220, Czech Republic

² Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, Prague 212843, Czech Republic

³ Department of Cell Biology, Faculty of Science, Charles University, Viničná 7, Prague 212843, Czech Republic

Molecules 2015, 20(2), 3463-3478; https://doi.org/10.3390/molecules20023463 - 17 Feb 2015

Cited by 6 | Viewed by 8226

Abstract

The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca²⁺-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal [...] Read more.

The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca²⁺-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal > Man. These findings established for rat Nkrp1a have been extrapolated to all additional Nkrp1 receptors and have been supported by numerous studies over the past two decades. However, since 1996 there has been controversy and another article showed lack of interactions with saccharides in 1999. Nevertheless, several high affinity saccharide ligands were synthesized in order to utilize their potential in antitumor therapy. Subsequently, protein ligands were introduced as specific binders for Nkrp1 proteins and three dimensional models of receptor/protein ligand interaction were derived from crystallographic data. Finally, for at least some members of the NK cell C-type lectin-like proteins, the “sweet story” was impaired by two reports in recent years. It has been shown that the rat Nkrp1a and CD69 do not bind saccharide ligands such as GlcNAc, GalNAc, chitotetraose and saccharide derivatives (GlcNAc-PAMAM) do not directly and specifically influence cytotoxic activity of NK cells as it was previously described. Full article

(This article belongs to the Special Issue Lectins)

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Molecules, Volume 20, Issue 2 (February 2015) – 97 articles , Pages 1755-3495

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