http://www.mdpi.com/journal/molecules Latest open access articles published in Molecules at http://www.mdpi.com/journal/molecules http://www.mdpi.com/1420-3049/18/5/6113 Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases. Molecules 2013-05-22 18 5 Article 10.3390/molecules18056113 6113 6127 1420-3049 2013-05-22 doi: 10.3390/molecules18056113 Su-Jin Kim Gil-Yong Lee Ji-Wook Jung Sa-Rang Oh Eun-Mi Ahn Sung-Hoon Kim Seung-Heon Hong Jae-Young Um http://www.mdpi.com/1420-3049/18/5/6101 The two step synthesis of a new bolaamphiphile derived from alkenyl l-rhamnosides was described. The general synthetic strategy of bolaamphiphiles derived from l-rhamnose was based on a previous work describing the synthesis of bolaamphiphiles derived from d-xylose. The conformational properties of this new compound were investigated by FTIR spectroscopy in an aqueous film in order to obtain a reference for further studies about the membrane-interacting properties. Moreover, the surface activity of this new bolaamphiphile was analyzed by Langmuir balance technology and was compared with that of the analogous bolaamphiphile derived from alkenyl D-xylosides. The findings indicate that the rhamnoside-based bolaform has an increased surface activity and a better ability to form aggregates than xyloside-based one. Molecules 2013-05-22 18 5 Short Note 10.3390/molecules18056101 6101 6112 1420-3049 2013-05-22 doi: 10.3390/molecules18056101 Sylvain Gatard Mehmet Nasir Magali Deleu Nadia Klai Vincent Legrand Sandrine Bouquillon http://www.mdpi.com/1420-3049/18/5/6092 Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL) peroxidation induced with Cu2+, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF) was also evaluated and correlated with its biflavonoid content. The flavanone-(3→8'')-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE50 of 12.36 μg/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC50 = 11.85 μg/mL). These results suggest that the BF is an excellent antioxidant. Molecules 2013-05-22 18 5 Article 10.3390/molecules18056092 6092 6100 1420-3049 2013-05-22 doi: 10.3390/molecules18056092 Edison Osorio Julián Londoño Jaume Bastida http://www.mdpi.com/1420-3049/18/5/6057 In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC50 value of 54.57 nM in the MEK1 binding assay. Molecules 2013-05-21 18 5 Article 10.3390/molecules18056057 6057 6091 1420-3049 2013-05-21 doi: 10.3390/molecules18056057 Chao Wang Hao Zhang Fengrong Xu Yan Niu Yun Wu Xin Wang Yihong Peng Jing Sun Lei Liang Ping Xu http://www.mdpi.com/1420-3049/18/5/6035 The aim of this work was to gain insight into the effect of food formulation on aroma release and perception, both of which playing an important role in food appreciation. The quality and quantity of retronasal aroma released during food consumption affect the exposure time of olfactory receptors to aroma stimuli, which can influence nutritional and hedonic characteristics, as well as consumption behaviors. In yogurts, fruit preparation formulation can be a key factor to modulate aroma stimulation. In this context, the impact of size and hardness of fruit pieces in fat-free pear yogurts was studied. Proton Transfer Reaction-Mass Spectrometry (PTR-MS) was used to allow sensitive and on-line monitoring of volatile odorous compound release in the breath during consumption. In parallel, a trained panel used sensory profile and Temporal Dominance of Sensations (TDS) methods to characterize yogurt sensory properties and their dynamic changes during consumption. Results showed that the size of pear pieces had few effects on aroma release and perception of yogurts, whereas fruit hardness significantly influenced them. Despite the fact that yogurts presented short and similar residence times in the mouth, this study showed that fruit preparation could be an interesting formulation factor to enhance exposure time to stimuli and thus modify food consumption behaviors. These results could be taken into account to formulate new products that integrate both nutritional and sensory criteria. Molecules 2013-05-21 18 5 Article 10.3390/molecules18056035 6035 6056 1420-3049 2013-05-21 doi: 10.3390/molecules18056035 Joshua Mesurolle Anne Saint-Eve Isabelle Déléris Isabelle Souchon http://www.mdpi.com/1420-3049/18/5/6021 D-Glucopyranose-derived and L-idopyranose-derived piperidine nitrones were synthesized in good overall yields through six-step reaction sequence starting from readily available 2,3,4,6-tetra-O-benzyl-D-glucopyranose. The method is efficient and could be general for the synthesis of aldohexose-derived piperidine nitrones which are precursors of piperidine iminosugars. Molecules 2013-05-21 18 5 Article 10.3390/molecules18056021 6021 6034 1420-3049 2013-05-21 doi: 10.3390/molecules18056021 Hui Zhao Wen-Bo Zhao Jian-She Zhu Yue-Mei Jia Chu-Yi Yu http://www.mdpi.com/1420-3049/18/5/6008 Hen egg-white lysozyme (LSZ) is currently used in the food industry to limit the proliferation of lactic acid bacteria spoilage in the production of wine and beer, and to inhibit butyric acid fermentation in hard and extra hard cheeses (late blowing) caused by the outgrowth of clostridial spores. The aim of this work was to evaluate how the enzyme activity in commercial preparations correlates to the enzyme concentration and can be affected by the presence of process-related impurities. Different analytical approaches, including turbidimetric assay, SDS-PAGE and HPLC were used to analyse 17 commercial preparations of LSZ marketed in different countries. The HPLC method adopted by ISO allowed the true LSZ concentration to be determined with accuracy. The turbidimetric assay was the most suitable method to evaluate LSZ activity, whereas SDS-PAGE allowed the presence of other egg proteins, which are potential allergens, to be detected. The analytical results showed that the purity of commercially available enzyme preparations can vary significantly, and evidenced the effectiveness of combining different analytical approaches in this type of control. Molecules 2013-05-21 18 5 Article 10.3390/molecules18056008 6008 6020 1420-3049 2013-05-21 doi: 10.3390/molecules18056008 Milena Brasca Stefano Morandi Tiziana Silvetti Veronica Rosi Stefano Cattaneo Luisa Pellegrino http://www.mdpi.com/1420-3049/18/5/5993 The anionic calixarenes para-sulphonatocalix[4]arene and 1,3-di-Ophosphonatocalix[ 4]arene, have been used to cap silver nanoparticles. The binding of these functional particles with regard to various serum albumins (bovine serum albumin, human serum albumin, porcine serum albumin and sheep serum albumin) has been studied by variable temperature fluorescence spectroscopy. The quenching of the fluorescence of the proteins was shown to vary as a function of the anionic calixarene capping molecule and also as a function of the origin of the serum albumin. It is thus possible to discriminate between the different species. Molecules 2013-05-21 18 5 Article 10.3390/molecules18055993 5993 6007 1420-3049 2013-05-21 doi: 10.3390/molecules18055993 Yannick Tauran Arnaud Brioude Beomjoon Kim Florent Perret Anthony Coleman http://www.mdpi.com/1420-3049/18/5/5980 Micheliolide (MCL) derivatives with etherification or esterification of the hydroxyl group at the C4 position were synthesized and evaluated for their activities against different acute myelogenous leukemia (AML) cell lines. These derivatives demonstrated comparable activities against AML cell lines HL-60 and doxorubicin resistant cell line HL-60/A. As to multi-drug resistant AML progenitor cells KG-1a, MCL and some of its derivatives maintained significant activities, and only 1.1–2.7 fold activity reductions were observed when compared with the activities against HL-60, while doxorubicin showed 20-fold activity reduction. Our study demonstrated that the C4 hydroxyl group of MCL might not only be a suitable position for structural modifications, but also be a starting point for the design of appropriate molecular probes to explore the specific targets in the progenitor cell line KG-1a. Molecules 2013-05-21 18 5 Article 10.3390/molecules18055980 5980 5992 1420-3049 2013-05-21 doi: 10.3390/molecules18055980 Wei-Wei Ma Qian-Qian Shi Ya-Hui Ding Jing Long Quan Zhang Yue Chen http://www.mdpi.com/1420-3049/18/5/5965 The effect of foliar salicylic acid (SA) applications (10−3 and 10−5 M) on activities of nitrate reductase, guaiacol peroxidase (POD), superoxide dismutases (SOD), catalase (CAT) and proline enzymes and physiological parameters was evaluated in two ginger varieties (Halia Bentong and Halia Bara) under greenhouse conditions. In both varieties, tested treatments generally enhanced photosynthetic rate and total dry weight. Photosynthetic rate increases were generally accompanied by increased or unchanged stomatal conductance levels, although intercellular CO2 concentrations of treated plants were typically lower than in controls. Lower SA concentrations were generally more effective in enhancing photosynthetic rate and plant growth. Exogenous application of SA increased antioxidant enzyme activities and proline content; the greatest responses were obtained in plants sprayed with 10–5 M SA, with significant increases observed in CAT (20.1%), POD (45.2%), SOD (44.1%) and proline (43.1%) activities. Increased CAT activity in leaves is naturally expected to increase photosynthetic efficiency and thus net photosynthesis by maintaining a constant CO2 supply. Our results support the idea that low SA concentrations (10–5 M) may induce nitrite reductase synthesis by mobilizing intracellular NO3− and can provide protection to nitrite reductase degradation in vivo in the absence of NO3–. Observed positive correlations among proline, SOD, CAT and POD activities in the studied varieties suggest that increased SOD activity was accompanied by increases in CAT and POD activities because of the high demands of H2O2 quenching. Molecules 2013-05-21 18 5 Article 10.3390/molecules18055965 5965 5979 1420-3049 2013-05-21 doi: 10.3390/molecules18055965 Ali Ghasemzadeh Hawa Jaafar http://www.mdpi.com/1420-3049/18/5/5954 The synthesis of nanoparticles has become a matter of great interest in recent times due to their various advantageous properties and applications in a variety of fields. The exploitation of different plant materials for the biosynthesis of nanoparticles is considered a green technology because it does not involve any harmful chemicals. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (BS, Sargassum muticum) water extract containing sulphated polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. The structural and properties of the Fe3O4-NPs were investigated by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy (FESEM), energy dispersive X-ray fluorescence spectrometry (EDXRF), vibrating sample magnetometry (VSM) and transmission electron microscopy. The average particle diameter as determined by TEM was found to be 18 ± 4 nm. X-ray diffraction showed that the nanoparticles are crystalline in nature, with a cubic shape. The nanoparticles synthesized through this biosynthesis method can potentially useful in various applications. Molecules 2013-05-21 18 5 Article 10.3390/molecules18055954 5954 5964 1420-3049 2013-05-21 doi: 10.3390/molecules18055954 Mahnaz Mahdavi Farideh Namvar Mansor Ahmad Rosfarizan Mohamad http://www.mdpi.com/1420-3049/18/5/5936 Several diterpenes with the labdane skeleton show biological activity, including antiproliferative effects. Most of the research work on bioactive labdanes has been carried out on naturally occurring diterpenes and semisynthetic derivatives, but much less is known on the effects of diterpene dimers. The aim of the present work was to synthesize dimeric diterpenes from the labdane imbricatolic acid using esters, ethers and the triazole ring as linkers. Some 18 new derivatives were prepared and the compounds were evaluated for antiproliferative activity on human normal fibroblasts (MRC-5) and the following human tumor cell lines: AGS, SK-MES-1, J82 and HL-60. The diethers 8–10, differing in the number of CH2 units in the linker, presented better antiproliferative activity with a maximum effect for the derivative 9. The best antiproliferative effect against HL-60 cells was found for compounds 3 and 17, with IC50 values of 22.3 and 23.2 μM, lower than that found for the reference compound etoposide (2.23 μM). The compounds 9, 17 and 11 were the most active derivatives towards AGS cells with IC50 values of 17.8, 23.4 and 26.1 μM. A free carboxylic acid function seems relevant for the effect as several of the compounds showed less antiproliferative effect after methylation. Molecules 2013-05-21 18 5 Article 10.3390/molecules18055936 5936 5953 1420-3049 2013-05-21 doi: 10.3390/molecules18055936 Mariano Pertino Cristina Theoduloz Marco Bastías Guillermo Schmeda-Hirschmann http://www.mdpi.com/1420-3049/18/5/5891 Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, quinones, and phenolics. This review aims to briefly summarize the structurally different metabolites produced by Alternaria fungi, as well as their occurrences, biological activities and functions. Some considerations related to synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi are also discussed. Molecules 2013-05-21 18 5 Review 10.3390/molecules18055891 5891 5935 1420-3049 2013-05-21 doi: 10.3390/molecules18055891 Jingfeng Lou Linyun Fu Youliang Peng Ligang Zhou http://www.mdpi.com/1420-3049/18/5/5858 Recently, there has been significant progress in the field of soft- and hard-X-ray imaging for a wide range of applications, both technically and scientifically, via developments in sources, optics and imaging methodologies. While one community is pursuing extensive applications of available X-ray tools, others are investigating improvements in techniques, including new optics, higher spatial resolutions and brighter compact sources. For increased image quality and more exquisite investigation on characteristic biological phenomena, contrast agents have been employed extensively in imaging technologies. Heavy metal nanoparticles are excellent absorbers of X-rays and can offer excellent improvements in medical diagnosis and X-ray imaging. In this context, the role of gold (Au) is important for advanced X-ray imaging applications. Au has a long-history in a wide range of medical applications and exhibits characteristic interactions with X-rays. Therefore, Au can offer a particular advantage as a tracer and a contrast enhancer in X-ray imaging technologies by sensing the variation in X-ray attenuation in a given sample volume. This review summarizes basic understanding on X-ray imaging from device set-up to technologies. Then this review covers recent studies in the development of X-ray imaging techniques utilizing gold nanoparticles (AuNPs) and their relevant applications, including two- and three-dimensional biological imaging, dynamical processes in a living system, single cell-based imaging and quantitative analysis of circulatory systems and so on. In addition to conventional medical applications, various novel research areas have been developed and are expected to be further developed through AuNP-based X-ray imaging technologies. Molecules 2013-05-17 18 5 Review 10.3390/molecules18055858 5858 5890 1420-3049 2013-05-17 doi: 10.3390/molecules18055858 Sungsook Ahn Sung Jung Sang Lee http://www.mdpi.com/1420-3049/18/5/5814 The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to encompass those metabolites with a vasodilator effect whose mechanism of action involved both vascular endothelium and arterial smooth muscle. The results obtained from our bibliographic search showed that over half of the isolated compounds have a mechanism of action involving the endothelium. Most of these bioactive metabolites cause vasodilation either by activating the nitric oxide/cGMP pathway or by blocking voltage-dependent calcium channels. Moreover, it was found that many compounds induced vasodilation by more than one mechanism. This review confirms that secondary metabolites, which include a significant group of compounds with extensive chemical diversity, are a valuable source of new pharmaceuticals useful for the treatment and prevention of cardiovascular diseases. Molecules 2013-05-17 18 5 Review 10.3390/molecules18055814 5814 5857 1420-3049 2013-05-17 doi: 10.3390/molecules18055814 Francisco Luna-Vázquez César Ibarra-Alvarado Alejandra Rojas-Molina Isela Rojas-Molina Miguel Zavala-Sánchez http://www.mdpi.com/1420-3049/18/5/5804 Dried root of Rehmannia glutinosa is a kidney-tonifying herbal medicine with a long history of safe use in traditional folk medicine for the treatment of joint diseases. This study was conducted to investigate prevention of bone loss by a standardized dried root of R. glutinosa in an ovariectomized (OVX) rat model of osteoporosis. The OVX groups were divided into five groups treated with distilled water, 17β-estradiol (E2 10 µg/kg, once daily, i.p) and dried root of R. glutinosa extracts (DRGE 30, 100, and 300 mg/kg, twice daily, p.o) for eight weeks. We measured the body, organs, and uterus weights, and femur and lumbar vertebrae bone mineral density (BMD), serum alkaline phosphatase (ALP), estradiol levels. The treatments with DRGE 300 mg/kg significantly inhibited BMD decrease in the femur and lumbar (17.5% and 16.4%, p < 0.05, respectively) by OVX without affecting the body, organs, and uterus weights. Also, serum ALP level in the DRGE 300 mg/kg treated group was significantly decreased, but the estradiol level did not change in serum of the DRGE 300 mg/kg treated group. These results show that DRGE is able to prevent OVX-induced bone loss without influencing hormones such as estrogen. Molecules 2013-05-17 18 5 Communication 10.3390/molecules18055804 5804 5813 1420-3049 2013-05-17 doi: 10.3390/molecules18055804 Dong Lim Yun Kim http://www.mdpi.com/1420-3049/18/5/5792 Rhizobium tropici is a Gram-negative bacterium that induces nodules and fixed atmospheric nitrogen in symbiotic association with Phaseolus vulgaris (common bean) and some other leguminous species. Lectins are proteins that specifically bind to carbohydrates and, consequently, modulate different biological functions. In this study, the d-glucose/ d-mannose-binding lectins (from seeds of Dioclea megacarpa, D. rostrata and D. violacea) and D-galactose-binding lectins (from seeds of Bauhinia variegata, Erythina velutina and Vatairea macrocarpa) were purified using chromatographic techniques and evaluated for their effect on the growth of R. tropici CIAT899. All lectins were assayed with a satisfactory degree of purity according to SDS-PAGE analysis, and stimulated bacterial growth; in particular, the Dioclea rostrata lectin was the most active among all tested proteins. As confirmed in the present study, both d-galactose- and d-glucose/d-mannose-binding lectins purified from the seeds of leguminous plants may be powerful biotechnological tools to stimulate the growth of R. tropici CIAT99, thus improving symbiotic interaction between rhizobia and common bean and, hence, the production of this field crop. Molecules 2013-05-17 18 5 Article 10.3390/molecules18055792 5792 5803 1420-3049 2013-05-17 doi: 10.3390/molecules18055792 Mayron de Vasconcelos Cláudio Cunha Francisco Arruda Victor Carneiro Rafaela Bastos Fábio Mercante Kyria Nascimento Benildo Cavada Ricardo Santos Edson Teixeira http://www.mdpi.com/1420-3049/18/5/5779 Dendrobium spp. are precious medicinal plants, used in China for thousands of years as health foods and nutrients. Polysaccharides are the main effective ingredients in Dendrobium plants. In this study, the chemical characteristics and the effects of crude polysaccharides (CPs) from five species of Dendrobium on macrophage function were investigated and compared in vitro for the first time. Chemical characteristic studies showed that CPs from different species of Dendrobium were diverse, displaying widely varied Mw distributions and molar ratios of monosaccharides. Their effects on macrophage functions, such as promoting phagocytosis, release of NO and cytokines IL-1α, IL-6, IL-10 and TNF-α, were also different. Moreover, CPs from D. officinale, especially collected from Yunnan Province, exerted the strongest immunomodulatory activities and could be explored as a novel potential functional food. The diverse chemical characteristics of CPs from different species of Dendrobium might contribute to their varied effects on macrophage functions, which should be further investigated. Molecules 2013-05-17 18 5 Article 10.3390/molecules18055779 5779 5791 1420-3049 2013-05-17 doi: 10.3390/molecules18055779 Lan-Zhen Meng Guang-Ping Lv De-Jun Hu Kit-Leong Cheong Jing Xie Jing Zhao Shao-Ping Li http://www.mdpi.com/1420-3049/18/5/5761 This manuscript describes the evaluation of anti-infective potential in vitro of organic extracts from nine sponges, one ascidian, two octocorals, one bryozoan, and 27 seaweed species collected along the Brazilian coast. Antimicrobial activity was tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231) by the disk diffusion method. Antiprotozoal activity was evaluated against Leishmania braziliensis (MHOM/BR/96/LSC96-H3) promastigotes and Trypanosoma cruzi (MHOM/BR/00/Y) epimastigotes by MTT assay. Activity against intracellular amastigotes of T. cruzi and L. brasiliensis in murine macrophages was also evaluated. Antiviral activity was tested against Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the plaque number reduction assay (IC50). Cytotoxicity on VERO cells was evaluated by the MTT assay (CC50). The results were expressed as SI = CC50/IC50. The most promising antimicrobial results were obtained against S. aureus and C. albicans with Dragmacidon reticulatum. Among the seaweeds, only Osmundaria obtusiloba showed moderate activity against P. aeruginosa. Concerning antiprotozoal activity, Bugula neritina, Carijoa riseii, Dragmaxia anomala and Haliclona (Halichoclona) sp. showed the most interesting results, mainly against extracellular promastigote forms of L. braziliensis (66, 35.9, 97.2, and 43.6% inhibition, respectively). Moreover, six species of seaweeds Anadyomene saldanhae, Caulerpa cupressoides, Canistrocarpus cervicornis, Dictyota sp., Ochtodes secundiramea, and Padina sp. showed promising results against L. braziliensis (87.9, 51.7, 85.9, 93.3, 99.7, and 80.9% inhibition, respectively), and only Dictyota sp. was effective against T. cruzi (60.4% inhibition). Finally, the antiherpes activity was also evaluated, with Haliclona (Halichoclona) sp. and Petromica citrina showing the best results (SI = 11.9 and SI > 5, respectively). All the active extracts deserve special attention in further studies to chemically characterize the bioactive compounds, and to perform more refined biological assays. Molecules 2013-05-16 18 5 Article 10.3390/molecules18055761 5761 5778 1420-3049 2013-05-16 doi: 10.3390/molecules18055761 Éverson Bianco Simone de Oliveira Caroline Rigotto Maiko Tonini Tatiana da Rosa Guimarães Francine Bittencourt Lidiane Gouvêa Cassandra Aresi Maria de Almeida Maria Moritz Cintia Martins Fernando Scherner João Carraro Paulo Horta Flávio Reginatto Mario Steindel Cláudia Simões Eloir Schenkel http://www.mdpi.com/1420-3049/18/5/5749 Oil-chitosan composite spheres were synthesized by encapsulation of sunflower seed oil in chitosan droplets, dropping into NaOH solution and in situ solidification. Hydrophilic materials (i.e., iron oxide nanoparticles) and lipophilic materials (i.e., rhodamine B or epirubicin) could be encapsulated simultaneously in the spheres in a one step process. The diameters of the prepared spheres were 2.48 ± 0.11 mm (pure chitosan spheres), 2.31 ± 0.08 mm (oil-chitosan composites), 1.49 ± 0.15 mm (iron-oxide embedded oil-chitosan composites), and 1.69 ± 0.1 mm (epirubicin and iron oxide encapsulated oil-chitosan composites), respectively. Due to their superparamagnetic properties, the iron-oxide embedded oil-chitosan composites could be guided by a magnet. A lipophilic drug (epirubicin) could be loaded in the spheres with encapsulation rate measured to be 72.25%. The lipophilic fluorescent dye rhodamine B was also loadable in the spheres with red fluorescence being observed under a fluorescence microscope. We have developed a novel approach to an in situ process for fabricating oil-chitosan composite spheres with dual encapsulation properties, which are potential multifunctional drug carriers. Molecules 2013-05-16 18 5 Article 10.3390/molecules18055749 5749 5760 1420-3049 2013-05-16 doi: 10.3390/molecules18055749 Keng-Shiang Huang Chih-Yu Wang Chih-Hui Yang Alexandru Grumezescu Yung-Sheng Lin Chao-Pin Kung I-Yin Lin Yi-Ching Chang Wei-Jie Weng Wei-Ting Wang http://www.mdpi.com/1420-3049/18/5/5736 As part of a program aiming at the selection of yeast strains which might be of interest as sources of natural flavours and fragrances, the bioreduction of (4R)-(−)-carvone and (1R)-(−)-myrtenal by whole-cells of non-conventional yeasts (NCYs) belonging to the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazachstania, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma and Wickerhamomyces was studied. Volatiles produced were sampled by means of headspace solid-phase microextraction (SPME) and the compounds were analysed and identified by gas chromatography–mass spectroscopy (GC-MS). Yields (expressed as % of biotransformation) varied in dependence of the strain. The reduction of both (4R)-(−)-carvone and (1R)-(−)-myrtenal were catalyzed by some ene-reductases (ERs) and/or carbonyl reductases (CRs), which determined the formation of (1R,4R)-dihydrocarvone and (1R)-myrtenol respectively, as main flavouring products. The potential of NCYs as novel whole-cell biocatalysts for selective biotransformation of electron-poor alkenes for producing flavours and fragrances of industrial interest is discussed. Molecules 2013-05-16 18 5 Article 10.3390/molecules18055736 5736 5748 1420-3049 2013-05-16 doi: 10.3390/molecules18055736 Marta Goretti Benedetta Turchetti Maria Cramarossa Luca Forti Pietro Buzzini http://www.mdpi.com/1420-3049/18/5/5723 Four new citrinin derivatives, including two citrinin dimers and two citrinin monomer derivatives, were isolated and identified from a marine-derived fungal strain Penicillium sp. ML226 along with six known related compounds. Their structures were elucidated by spectroscopic and chemical methods. The new compounds showed modest cytotoxic activity against HepG-2 cell line and weak antimicrobial activity against Staphylococcus aureus. Molecules 2013-05-16 18 5 Article 10.3390/molecules18055723 5723 5735 1420-3049 2013-05-16 doi: 10.3390/molecules18055723 Mei Wang Chun Lu Qing Xu Si Song Zhi Hu Zhong Zheng http://www.mdpi.com/1420-3049/18/5/5706 Proteolytic cleavage of amyloid precursor protein by β-secretase (BACE1) is a key step in generating the N-terminal of β-amyloid (Aβ), which further forms into amyloid plaques that are considered as the hallmark of Alzheimer’s disease. Inhibitors of BACE1 can reduce the levels of Aβ and thus have a therapeutic potential for treating the disease. We report here the identification of a series of small molecules bearing an indole acylguanidine core structure as potent BACE1 inhibitors. The initial weak fragment was discovered by virtual screening, and followed with a hit-to-lead optimization. With the aid of co-crystal structures of two discovered inhibitors (compounds 19 and 25) with BACE1, we explored the SAR around the indole and aryl groups, and obtained several BACE1 inhibitors about 1,000-fold more potent than the initial fragment hit. Accompanying the lead optimization, a previously under-explored sub-site opposite the flap loop was redefined as a potential binding site for later BACE1 inhibitor design. Molecules 2013-05-16 18 5 Article 10.3390/molecules18055706 5706 5722 1420-3049 2013-05-16 doi: 10.3390/molecules18055706 Yiquan Zou Li Li Wuyan Chen Tiantian Chen Lanping Ma Xin Wang Bing Xiong Yechun Xu Jingkang Shen http://www.mdpi.com/1420-3049/18/5/5697 The trace impurities discovered after extended storage of a 5-amino- benzimidazole library were determined as imidazo[4,5-g]quinazoline derivatives by extensive spectroscopic data analysis. The formation of this highly aromatic heterocyclic ring involved a novel multi-component reaction, using which several novel compounds were prepared. Its mechanism was deduced as a cascade of chemical transformations, including the formation of a Schiff’s base, intramolecular hetero-Diels-Alder reaction, defluorination and dehydrogenation. Molecules 2013-05-16 18 5 Article 10.3390/molecules18055697 5697 5705 1420-3049 2013-05-16 doi: 10.3390/molecules18055697 Li Li Qianqian Zhang Bo Liu Gang Liu http://www.mdpi.com/1420-3049/18/5/5684 The aim of this research was to determine the chemical composition of the essential oil of Acorus calamus rhizomes, its insecticidal activity against the booklouse, (Liposcelis bostrychophila) and to isolate any insecticidal constituents from the essential oil. The essential oil of A. calamus rhizomes was obtained by hydrodistillation and analyzed by GC-FID and GC-MS. A total of 32 components of the essential oil of A. calamus rhizomes was identified and the principal compounds in the essential oil were determined to be α-asarone (50.09%), (E)-methylisoeugenol (14.01%), and methyleugenol (8.59%), followed by β-asarone (3.51%), α-cedrene (3.09%) and camphor (2.42%). Based on bioactivity-guided fractionation, the three active constituents were isolated from the essential oil and identified as methyleugenol, (E)-methylisoeugenol and α-asarone. The essential oil exhibited contact toxicity against L. bostrychophila with an LD50 value of 100.21 µg/cm2 while three constituent compounds, α-asarone, methyleugenol, and (E)-methylisoeugenol had LD50 values of 125.73 µg/cm2, 103.22 µg/cm2 and 55.32 µg/cm2, respectively. Methyleugenol and (E)-methylisoeugenol possessed fumigant toxicity against L. bostrychophila adults with LC50 values of 92.21 μg/L air and 143.43 μg/L air, respectively, while the crude essential oil showed an LC50 value of 392.13 μg/L air. The results indicate that the essential oil of A. calamus rhizomes and its constituent compounds have potential for development into natural fumigants/insecticides for control of the booklice. Molecules 2013-05-15 18 5 Article 10.3390/molecules18055684 5684 5696 1420-3049 2013-05-15 doi: 10.3390/molecules18055684 Xin Liu Li Zhou Zhi Liu Shu Du http://www.mdpi.com/1420-3049/18/5/5669 Eighteen (3R) and (3R,4R)-N-phenyl-, N-phenylalkyl and N-arylsuccinimides were prepared with high enantioselectivity by biotransformation of maleimides with A. fumigatus. This environmentally friendly, clean and economical procedure was performed by the whole-cell fungal bioconversion methodology. Their corresponding eighteen racemic succinimides were prepared instead by synthetic methods. Both, the racemic and the chiral succinimides were tested simultaneously by the microbroth dilution method of CLSI against a panel of human opportunistic pathogenic fungi of clinical importance. Chiral succinimides showed higher antifungal activity than the corresponding racemic ones and the differences in activity were established by statistical methods. The bottlenecks for developing chiral drugs are how to obtain them through a low-cost procedure and with high enantiomeric excess. Results presented here accomplish both these objectives, opening an avenue for the development of asymmetric succinimides as new antifungal drugs for pharmaceutical use. Molecules 2013-05-15 18 5 Article 10.3390/molecules18055669 5669 5683 1420-3049 2013-05-15 doi: 10.3390/molecules18055669 Maximiliano Sortino Agustina Postigo Susana Zacchino http://www.mdpi.com/1420-3049/18/5/5648 A water-soluble indocarbocyanine dye was synthesized and its photophysics were studied for the first time on two solid hosts, microcrystalline cellulose and b-cyclodextrin, as well as in homogeneous media. The inclusion of the indocarbocyanine moiety onto microcrystalline cellulose increased the dye aggregation with both H and J aggregates being formed. Adsorption on b-cyclodextrin enhanced aggregation in a similar way. The fluorescence quantum yields were determined for the powdered samples of the cyanine dye on the two hosts and a significant increase was observed relative to homogeneous solution. A remarkable concentration dependence was also detected in both cases. A lifetime distribution analysis has shown that the indocarbocyanine dye mainly occupies the amorphous part of cellulose and is not entrapped in the crystalline part of this host. In the b-CD case, the adsorption occurs outside the host cavity. In both hosts a strong concentration quenching effect is observed and only monomers emit. Both adsorptions may be explained by stereochemical constraints imposed by the two long sulphoethyl tails linked to nitrogen atoms of the indocarbocyanine dye. Molecules 2013-05-15 18 5 Article 10.3390/molecules18055648 5648 5668 1420-3049 2013-05-15 doi: 10.3390/molecules18055648 Reda El-Shishtawy Anabela Oliveira Paulo Almeida Diana Ferreira David Conceição Luis Ferreira http://www.mdpi.com/1420-3049/18/5/5611 Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic proteins have been shown to stimulate bone repair. However, there are a number of drawbacks associated with viral and synthetic non-viral gene delivery approaches. One natural polymer which has generated interest as a gene delivery vector is chitosan. Chitosan is biodegradable, biocompatible and non-toxic. Much of the appeal of chitosan is due to the presence of primary amine groups in its repeating units which become protonated in acidic conditions. This property makes it a promising candidate for non-viral gene delivery. Chitosan-based vectors have been shown to transfect a number of cell types including human embryonic kidney cells (HEK293) and human cervical cancer cells (HeLa). Aside from its use in gene delivery, chitosan possesses a range of properties that show promise in tissue engineering applications; it is biodegradable, biocompatible, has anti-bacterial activity, and, its cationic nature allows for electrostatic interaction with glycosaminoglycans and other proteoglycans. It can be used to make nano- and microparticles, sponges, gels, membranes and porous scaffolds. Chitosan has also been shown to enhance mineral deposition during osteogenic differentiation of MSCs in vitro. The purpose of this review is to critically discuss the use of chitosan as a gene delivery vector with emphasis on its application in orthopedic tissue engineering. Molecules 2013-05-15 18 5 Review 10.3390/molecules18055611 5611 5647 1420-3049 2013-05-15 doi: 10.3390/molecules18055611 Rosanne Raftery Fergal O'Brien Sally-Ann Cryan http://www.mdpi.com/1420-3049/18/5/5594 Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET). To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c.) Lewis lung carcinoma (LLC) mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide. Molecules 2013-05-15 18 5 Article 10.3390/molecules18055594 5594 5610 1420-3049 2013-05-15 doi: 10.3390/molecules18055594 Cam Patterson C. Frederick Hong Yuan Laura Dyer Pamela Lockyer David Lalush Anka Veleva http://www.mdpi.com/1420-3049/18/5/5580 A hexachlorocyclotriphosphazene (HCCP)-mediated direct formation of quinazoline (thio)ethers from quinazolin-4(3H)-ones has been developed. Treatment of quinazolin-4(3H)-ones with HCCP, diisopropylethylamine (DIPEA), and thiophenols resulted in formation of the corresponding 4-arylthioquinazoline derivatives in moderate to excellent yields. This method has also been utilized to prepare 4-aryloxyquinazoline and 4-alkoxyquinazoline derivatives using phenols and sodium alkoxides as the nucleophiles. Molecules 2013-05-15 18 5 Article 10.3390/molecules18055580 5580 5593 1420-3049 2013-05-15 doi: 10.3390/molecules18055580 Baoxiang Hu Xiaochu Zhang Lili Sheng Ming Guo Zhenlu Shen Xinquan Hu Nan Sun Weimin Mo http://www.mdpi.com/1420-3049/18/5/5568 Three new multiflorane-type triterpenes; 7a-methoxymultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (1), 7-oxomultiflor-8-ene-3a,29-diol 3-acetate-29-benzoate (2), and multiflora-7,9(11)-diene-3a,29-diol 3-p-hydroxybenzoate-29-benzoate (3), were isolated from seeds of Cucurbita maxima, along with three known compounds. Compound 3 and multiflora-7,9(11)-diene-3a-29-diol 3-benzoate (5) exhibited potent inhibitory effects on melanogenesis, with low cytotoxicities, and 2 exhibited single-digit micromolar cytotoxicity against HL-60 and P388 cells. Molecules 2013-05-14 18 5 Article 10.3390/molecules18055568 5568 5579 1420-3049 2013-05-14 doi: 10.3390/molecules18055568 Takashi Kikuchi Mika Takebayashi Mayumi Shinto Takeshi Yamada Reiko Tanaka http://www.mdpi.com/1420-3049/18/5/5543 Kinetic Isotope effects (KIEs) have long served as a probe for the mechanisms of both enzymatic and solution reactions. Here, we discuss various models for the physical sources of KIEs, how experimentalists can use those models to interpret their data, and how the focus of traditional models has grown to a model that includes motion of the enzyme and quantum mechanical nuclear tunneling. We then present two case studies of enzymes, thymidylate synthase and alcohol dehydrogenase, and discuss how KIEs have shed light on the C-H bond cleavages those enzymes catalyze. We will show how the combination of both experimental and computational studies has changed our notion of how these enzymes exert their catalytic powers. Molecules 2013-05-14 18 5 Review 10.3390/molecules18055543 5543 5567 1420-3049 2013-05-14 doi: 10.3390/molecules18055543 Daniel Roston Zahidul Islam Amnon Kohen http://www.mdpi.com/1420-3049/18/5/5531 Water extractable arabinoxylan (WEAX) aerogels were prepared by extracting the solvent from the alcogels (WEAX hydrogels with an alcohol as the solvent) with carbon dioxide under supercritical conditions. WEAX aerogels were characterized using scanning electron microscopy and adsorption and desorption nitrogen isotherms. The micrographs indicate a heterogeneous porous network structure in WEAX aerogel. Adsorption/desorption nitrogen isotherms of this material were type IV, which confirm that this material possess a mesoporous structure. WEAX aerogels rehydration capability was evaluated and the water absorption mechanism was determined. The WEAX aerogels water absorption mechanism was non-Fickian (n = 0.54). Molecules 2013-05-14 18 5 Article 10.3390/molecules18055531 5531 5542 1420-3049 2013-05-14 doi: 10.3390/molecules18055531 Jorge Marquez-Escalante Elizabeth Carvajal-Millan Mario Miki-Yoshida Lorena Alvarez-Contreras Alma Toledo-Guillén Jaime Lizardi-Mendoza Agustín Rascón-Chu http://www.mdpi.com/1420-3049/18/5/5517 The synthesis of a newangular analog 11 of cyclozonarone was achieved via Diels-Alder reaction between a sesquiterpene-1,3-diene and 1,4-benzoquinone. The cytotoxic activity of ent-cyclozonarone [(+)-10] and the angular (−)-cyclozonarone analog 11 has been determined in three human cancer cell lines and in normal fibroblasts using the sulforhodamine B assay. The analyzed isomers induce cell death in different cancer cell lines by eliciting nuclear condensation and fragmentation, decreasing mitochondrial membrane permeability and increasing caspase-3 activity, all traits indicating apoptosis, with the effects of (+)-10 being stronger than those of 11 in all cases. Molecules 2013-05-13 18 5 Article 10.3390/molecules18055517 5517 5530 1420-3049 2013-05-13 doi: 10.3390/molecules18055517 Natalia Sobarzo Iván Venegas Cristian Sánchez Luis Catalán Cristóbal Rojas Valentina Valdivia Joan García Mauricio Fritis http://www.mdpi.com/1420-3049/18/5/5498 A series of novel 3-benzisoxazolyl-4-indolyl-maleimides were synthesized and evaluated for their GSK-3β inhibitory activity. Most compounds exhibited high inhibitory potency towards GSK-3β. Among them, compound 7j with an IC50 value of 0.73 nM was the most promising GSK-3β inhibitor. Preliminary structure-activity relationships were examined and showed that different substituents on the indole ring and N1-position of the indole ring had varying degrees of influence on the GSK-3β inhibitory potency. Compounds 7c, 7f, 7j–l and 7o–q could obviously reduce Aβ-induced Tau hyperphosphorylation by inhibiting GSK-3β in a cell-based functional assay. Molecules 2013-05-13 18 5 Article 10.3390/molecules18055498 5498 5516 1420-3049 2013-05-13 doi: 10.3390/molecules18055498 Qing Ye Meng Li Yubo Zhou Tao Pang Lei Xu Jiayi Cao Liang Han Yujin Li Weisi Wang Jianrong Gao Jia Li http://www.mdpi.com/1420-3049/18/5/5482 New hetaryl- and alkylidenerhodanine derivatives 3a–d, 3e, and 4a–d were prepared from heterocyclic aldehydes 1a–d or acetaldehyde 1e. The treatment of several rhodanine derivatives 3a–d and 3e with piperidine or morpholine in THF under reflux, afforded (Z)-5-(hetarylmethylidene)-2-(piperidin-1-yl)thiazol-4(5H)-ones and 2-morpholinothiazol-4(5H)-ones 5a–d, 6a–d, and (Z)-5-ethylidene-2-morpholinothiazol-4(5H)-one (5e), respectively, in good yields. Structures of all compounds were determined by IR, 1D and 2D NMR and mass spectrometry. Several of these compounds were screened by the U.S. National Cancer Institute (NCI) to assess their antitumor activity against 60 different human tumor cell lines. Compound 3c showed high activity against HOP-92 (Non-Small Cell Lung Cancer), which was the most sensitive cell line, with GI50 = 0.62 μM and LC50 > 100 μM from the in vitro assays. In vitro antifungal activity of these compounds was also determined against 10 fungal strains. Compound 3e showed activity against all fungal strains tested, but showed high activity against Saccharomyces cerevisiae (MIC 3.9 μg/mL). Molecules 2013-05-13 18 5 Article 10.3390/molecules18055482 5482 5497 1420-3049 2013-05-13 doi: 10.3390/molecules18055482 Alberto Insuasty Juan Ramírez Marcela Raimondi Carlos Echeverry Jairo Quiroga Rodrigo Abonia Manuel Nogueras Justo Cobo María Rodríguez Susana Zacchino Braulio Insuasty http://www.mdpi.com/1420-3049/18/5/5472 Enantioselective esterification of ibuprofen has been successfully carried out in an organic solvent catalyzed by recombinant APE 1547 (a thermophilic esterase from the archaeon Aeropyrum pernix K1). Here we used microwave irradiation (MW) as the mode of heating to improve the enzyme performance. Under the optimum conditions, the enzyme activity of APE 1547 was 4.16 μmol/mg/h and the enantioselectivity (E value) was 52.9. Compared with conventional heating, the enzyme activity and the enantioselectivity were increased about 21.9-fold and 1.4-fold, respectively. The results also indicated that APE 1547 can maintain 95% of its activity even after being used five times, suggesting that the enzyme is stable under low power MW conditions. Molecules 2013-05-13 18 5 Article 10.3390/molecules18055472 5472 5481 1420-3049 2013-05-13 doi: 10.3390/molecules18055472 Zecheng Yang Xuedun Niu Xuedong Fang Ge Chen Hong Zhang Hong Yue Lei Wang Dantong Zhao Zhi Wang http://www.mdpi.com/1420-3049/18/5/5455 The aim of this study was to develop novel transdermal films of ondansetron HCl with high molecular weight chitosan as matrix polymer and 2-(2-ethoxy-ethoxy) ethanol (Transcutol®) as plasticizer. In this context, firstly the physicochemical properties of gels used to formulate transdermal films were characterized and, physicochemical properties and bioadhesiveness of the transdermal films prepared with chitosan gels were assessed. The impact of three different types of terpenes, namely limonene, nerolidol and eucalyptol on in vitro skin permeation of ondansetron from transdermal films were also examined. ATR-FTIR measurements were performed to investigate the effects of the chitosan film formulations on in vitro conformational order of stratum corneum intercellular lipids after 24 h permeation study. The results showed that the chitosan gels consisting of Transcutol® as plasticizer and terpenes as penetration enhancer may be used to prepare transdermal films of ondansetron due to the good mechanical properties and bioadhesiveness of the transdermal films. Eucalyptol (1%) showed higher permeation enhancer effect than the other terpenes and control. ATR-FTIR data confirmed that finding in which eucalyptol induced a blue shift in the both CH2 asymmetric and symmetric absorbance peak positions indicating increased lipid fluidity of stratum corneum. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055455 5455 5471 1420-3049 2013-05-10 doi: 10.3390/molecules18055455 Aslı Can Meryem Erdal Sevgi Güngör Yıldız Özsoy http://www.mdpi.com/1420-3049/18/5/5434 The fragrant camphor tree (Cinnamomum camphora) and its products, such as camphor oil, have been coveted since ancient times. Having a rich history of traditional use, it was particularly used as a fumigant during the era of the Black Death and considered as a valuable ingredient in both perfume and embalming fluid. Camphor has been widely used as a fragrance in cosmetics, as a food flavourant, as a common ingredient in household cleaners, as well as in topically applied analgesics and rubefacients for the treatment of minor muscle aches and pains. Camphor, traditionally obtained through the distillation of the wood of the camphor tree, is a major essential oil component of many aromatic plant species, as it is biosynthetically synthesised; it can also be chemically synthesised using mainly turpentine as a starting material. Camphor exhibits a number of biological properties such as insecticidal, antimicrobial, antiviral, anticoccidial, anti-nociceptive, anticancer and antitussive activities, in addition to its use as a skin penetration enhancer. However, camphor is a very toxic substance and numerous cases of camphor poisoning have been documented. This review briefly summarises the uses and synthesis of camphor and discusses the biological properties and toxicity of this valuable molecule. Molecules 2013-05-10 18 5 Review 10.3390/molecules18055434 5434 5454 1420-3049 2013-05-10 doi: 10.3390/molecules18055434 Weiyang Chen Ilze Vermaak Alvaro Viljoen http://www.mdpi.com/1420-3049/18/5/5420 A series of new matrinic acid derivatives 5a–e was synthesized. The chemical structures of the synthesized compounds were confirmed by 1H-NMR, 13C-NMR, and electrospray ionization mass spectroscopy. The anti-tumor activities were also investigated in vitro by evaluating the effect of synthesized compounds on the proliferation of A375, A549, HeLa, and HepG2 cells. Compound 5e was found to be the most potent against A375 and HeLa cells, with IC50 values of 37 and 75.5 μg/mL, respectively. Compounds 5b, 5c, 5g, and 5h also exhibited antiproliferative activities against A549 cells, with IC50 values within the 36.2–47 μg/mL range. For HepG2 cells, 5e and 5i, with IC50 values of 78.9 and 61 μg/mL, respectively, showed higher antiproliferative activity than taxol. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055420 5420 5433 1420-3049 2013-05-10 doi: 10.3390/molecules18055420 Fan Chao Dong-En Wang Rui Liu Qin Tu Jian-Jun Liu Jinyi Wang http://www.mdpi.com/1420-3049/18/5/5405 Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055405 5405 5419 1420-3049 2013-05-10 doi: 10.3390/molecules18055405 Seoung Shin Eunsun Jung Seungbeom Kim Kyung-Eun Lee Jong-Kyung Youm Deokhoon Park http://www.mdpi.com/1420-3049/18/5/5389 Curcumin is the major phenolic compound present in turmeric (Curcuma longa L.). Curcumin and 15 novel analogs were investigated for their antioxidant and selected biological activities. Strong relationships between the structure and evaluated activity revealed that the compounds with specific functional groups and carbon skeleton had specific biological profiles. Among the compounds tested, the derivatives (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e), and (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)-cyclopentanone (3d) and the parent compound curcumin exhibited the strongest free radical scavenging and antioxidant capacity. Concerning the other biological activities studied the compound (E)-2-(4-hydroxy-3-methoxybenzylidene)-5-((E)-3-(4-hydroxy-3-methoxy-phenyl)-acryloyl)cyclopentanone (3d) was the most potent angiotensin converting enzyme (ACE) inhibitor, while the derivatives (E)-2-(4-hydroxybenzylidene)-6-((E)-3-(4-hydroxyphenyl)acryloyl)cyclohexanone (2b), (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclohexanone (2e) and (E)-2-(3,4-dimethoxybenzylidene)-5-((E)-3-(3,4-dimethoxyphenyl)acryloyl)cyclopentanone (3e) exhibited strong tyrosinase inhibition. Moreover, (E)-2-(3,4-dimethoxybenzylidene)-6-((E)-3-(3,4-dimethoxyphenyl)-acryloyl)cyclohexanone (2e) was also found to be the strongest human HIV-1 protease inhibitor in vitro among the tested compounds. Cytotoxicity studies using normal human lung cells revealed that the novel curcumin as well as its carbocyclic analogs are not toxic. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055389 5389 5404 1420-3049 2013-05-10 doi: 10.3390/molecules18055389 Khushwant Bhullar Amitabh Jha Dani Youssef H. Rupasinghe http://www.mdpi.com/1420-3049/18/5/5373 Chalcogenide glasses are based on sulfur, selenium and tellurium elements, and have been studied for several decades regarding different applications. Among them, selenide glasses exhibit excellent infrared transmission in the 1 to 15 µm region. Due to their good thermo-mechanical properties, these glasses could be easily shaped into optical devices such as lenses and optical fibers. During the past decade of research, selenide glass fibers have been proved to be suitable for infrared sensing in an original spectroscopic method named Fiber Evanescent Wave Spectroscopy (FEWS). FEWS has provided very nice and promising results, for example for medical diagnosis. Then, some sophisticated fibers, also based on selenide glasses, were developed: rare-earth doped fibers and microstructured fibers. In parallel, the study of telluride glasses, which can have transmission up to 28 µm due to its atom heaviness, has been intensified thanks to the DARWIN mission led by the European Space Agency (ESA). The development of telluride glass fiber enables a successful observation of CO2 absorption band located around 15 µm. In this paper we review recent results obtained in the Glass and Ceramics Laboratory at Rennes on the development of selenide to telluride glass optical fibers, and their use for spectroscopy from the mid to the far infrared ranges. Molecules 2013-05-10 18 5 Review 10.3390/molecules18055373 5373 5388 1420-3049 2013-05-10 doi: 10.3390/molecules18055373 Shuo Cui Radwan Chahal Catherine Boussard-Plédel Virginie Nazabal Jean-Louis Doualan Johann Troles Jacques Lucas Bruno Bureau http://www.mdpi.com/1420-3049/18/5/5360 Tetrabromobisphenol A (TBBPA), a commonly used brominated flame retardant, also functions as an endocrine disruptor. Thus, the degradation of TBBPA has attracted considerable interest among the scientific community. Iron(III)-porphyrin complexes are generally regarded as “green” catalysts and have been reported to catalyze the efficient degradation and dehalogenation of halogenated phenols in environmental wastewaters. However, they are quickly deactivated due to self-degradation in the presence of an oxygen donor, such as KHSO5. In the present study, an iron(III)-tetrakis (p-sulfonatophenyl)-porphyrin (FeTPPS) was immobilized on imidazole-modified silica (FeTPPS/IPS) via coordination of the Fe(III) with the nitrogen atom in imidazole to suppress self-degradation and thus enhance the catalyst reusability. The oxidative degradation and debromination of TBBPA and the influence of humic acid (HA), a major component in leachates, on the oxidation of TBBPA was investigated. More than 95% of the TBBPA was degraded in the pH range from 3 to 8 in the absence of HA, while the optimal pH for the reaction was at pH 8 in the presence of HA. Although the rate of degradation was decreased in the presence of HA, over 95% of the TBBPA was degraded within 12 h in the presence of 28 mg-C L−1 of HA. At pH 8, the FeTPPS/IPS catalyst could be reused up to 10 times without any detectable loss of activity for TBBPA for degradation and debromination, even in the presence of HA. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055360 5360 5372 1420-3049 2013-05-10 doi: 10.3390/molecules18055360 Qianqian Zhu Yusuke Mizutani Shohei Maeno Masami Fukushima http://www.mdpi.com/1420-3049/18/5/5348 In this study, we examined the cytotoxic effects of seven ent-labdane derivatives 1–7 (0–100 μM) in different human cancer cell lines. Our results showed that compounds 1–3 exhibited significant dose-dependent inhibition on the growth of the three different human cell lines, according to the sulphorhodamine B assay and produced morphological changes consistent with apoptosis, as confirmed by Hoestch 3342 staining analysis. They induced apoptosis in various cancer cell lines, as shown by nuclear condensation and fragmentation and caspase 3 activation. Such induction was associated with the depletion of mitochondrial membrane potential. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, the compounds showed potent proapoptotic effects on the two different cancer cell lines, suggesting that the compounds deserve more extensive investigation of their potential medicinal applications. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055348 5348 5359 1420-3049 2013-05-10 doi: 10.3390/molecules18055348 Joan Villena Alejandro Madrid Iván Montenegro Enrique Werner Mauricio Cuellar Luis Espinoza http://www.mdpi.com/1420-3049/18/5/5335 2-[18F]Fluoroethyl azide ([18F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [18F]fluoride (half-life 110 min), and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [18F]FEA is typically required, which is time-consuming and unpractical for routine applications. In addition, copper(I)-catalyzed cycloaddition of [18F]FEA with non-activated alkynes, and with substrates containing labile functional groups, can be challenging. Herein, we report a highly efficient and practical ligand-accelerated one-pot/two-step method for ‘click’ labeling of small molecule tracers with [18F]FEA. The method exploits the ability of the copper(I) ligand bathophenanthrolinedisulfonate to accelerate the rate of the cycloaddition reaction. As a result, alkynes can be added directly to the crude reaction mixture containing [18F]FEA, and as cyclisation occurs almost immediately at room temperature, the reaction is tolerant to labile functional groups. The method was demonstrated by reacting [18F]FEA with a series of alkyne-functionalized 6-halopurines to give the corresponding triazoles in 55–76% analytical radiochemical yield. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055335 5335 5347 1420-3049 2013-05-10 doi: 10.3390/molecules18055335 Eva Galante Bent Schoultz Matthias Koepp Erik Årstad http://www.mdpi.com/1420-3049/18/5/5326 Nine known compounds: trans-cinnamic acid, catechin, syringin, epicatechin, symplocoside, kaempferol 3-O-rhamnoside 7-O-glucoside, isovitexin 2-O-rhamnoside, herbacetin 7-O-glucoside, and pollenitin B and a new flavonoid glycoside, characterized as herbacetin 7-O-neohesperidoside (1) on the basis of spectroscopic analysis and chemical evidence, were isolated from a traditional crude drug, “Ephedra herb extract”. Compound 1 had no effects on HGF-induced motility, whereas herbacetin, which is an aglycone of 1, significantly inhibited it. Molecules 2013-05-10 18 5 Article 10.3390/molecules18055326 5326 5334 1420-3049 2013-05-10 doi: 10.3390/molecules18055326 Yoshiaki Amakura Morio Yoshimura Saori Yamakami Takashi Yoshida Daigo Wakana Masashi Hyuga Sumiko Hyuga Toshihiko Hanawa Yukihiro Goda http://www.mdpi.com/1420-3049/18/5/5317 Changes in the volatile components of unpasteurized and pasteurized makgeolli during 30 days of storage were investigated by gas chromatography-mass spectrometry (GC-MS) and GC-olfactometry (GC-O). A total of 11 odor-active compounds such as 3-methyl-1-butanol (isoamyl alcohol), 2-methyl-1-butanol, 2,3-butanediol, butanoic acid, 3-methylbutanoic acid (isovaleric acid), 2-methylbutanoic acid, 3-(methylthio)-1-propanol (methionol), 2-phenylethanol, ethyl decanoate, ethyl dodecanoate, and ethyl tetradecanoate were determined in both the pasteurized and unpasteurized makgeolli during 30 days of storage. Although there were no significant differences in the concentrations of odor-active compounds at the initial storage time, most of odor-active compounds were more significantly increased in unpasteurized makgeolli compared to the pasteurized one during the storage period. Molecules 2013-05-08 18 5 Article 10.3390/molecules18055317 5317 5325 1420-3049 2013-05-08 doi: 10.3390/molecules18055317 Hye-Jung Park Sang Lee Sang Song Young-Suk Kim http://www.mdpi.com/1420-3049/18/5/5306 Pulsatilla koreana, a species endemic to Korea, is an important herb used in traditional medicine to treat amoebic dysentery and malaria. In the present study, 23 oleanane-type triterpenoid saponins 1–23 and eight lupane-type triterpenoid saponins 24–31 were isolated from the roots of P. koreana. Their structures were elucidated on the basis of spectroscopic data. The methanol extract and isolated compounds were next assessed for nematicidal activity against the root-knot nematode (Meloidogyne incognita). The methanol extract showed strong nematicidal activity after 48 h, with a LC50 value of 92.8 μg/mL. Compounds 2, 5, 9, 20, and 21 showed significant effects, with LC50 values ranging from 70.1 to 94.7 μg/mL after 48 h. These results suggest that triterpenoid saponins from P. koreana should be explored as potential natural nematicides for developing new agents to control root-knot nematode disease Molecules 2013-05-08 18 5 Article 10.3390/molecules18055306 5306 5316 1420-3049 2013-05-08 doi: 10.3390/molecules18055306 Wei Li Ya Sun Xi Yan Seo Yang Suk Lee Hyo Byun Chang Moon Byung Han Young Kim http://www.mdpi.com/1420-3049/18/5/5288 Chitosan-grafted-poly(4-vinylpyridine) (Cs-PVP) copolymers could be synthesized under heterogeneous conditions in presence of a potassium persulfate and sodium sulfite redox system. The synthesized graft copolymer could be utilized effectively, in the form of beads, as an efficient catalyst for Michael additions of active methylenes to functionally substituted alkenes. Moreover, methyl moiety oxidation in methyl pyridazinyl carbonitriles by H2O2 in the presence of chitosan-g-polyvinyl pyridine–supported iron (III) complex, Cs-PVP/Fe, could be affected. A variety of pyrans, naphthopyrans, and thiopyrans could be synthesized efficiently in the presence of these graft copolymer beads by novel catalytic routes. These polymeric catalysts could be used instead of the old toxic commercial organic basic catalysts, piperidine or pyridine, and could be readily isolated from the reaction mixture and recycled several times without significant loss of catalytic activity. Molecules 2013-05-08 18 5 Article 10.3390/molecules18055288 5288 5305 1420-3049 2013-05-08 doi: 10.3390/molecules18055288 Khaled Khalil Hamad Al-Matar http://www.mdpi.com/1420-3049/18/5/5265 Six new phenolic compounds, named smiglabrone A (1), smiglabrone B (2), smilachromanone (3), smiglastilbene (4), smiglactone (5), smiglabrol (6), together with fifty-seven known ones 7–63 were isolated from the rhizomes of Smilax glabra. Their structures were elucidated on the basis of extensive spectroscopic analyses, as well as by comparison with literature data. Twenty-seven of these compounds were obtained from and identified in the genus Smilax for the first time. The absolute configuration of (2S)-1,2-O-di-trans-p-coumaroylglycerol (43) was determined for the first time using the exciton-coupled circular dichroism (ECCD) method. Thirty isolated compounds were evaluated for their antimicrobial activity against three Gram-negative bacteria, three Gram-positive bacteria and one fungus, and the corresponding structure-activity relationships were also discussed. Eighteen compounds were found to be antimicrobial against the microorganisms tested and the minimum inhibitory concentrations (MIC) were in the range of 0.0794–3.09 mM. Among them, compound 1 showed antimicrobial activity against Canidia albicans with MIC value of 0.146 mM, which was stronger than cinchonain Ia with an MIC of 0.332 mM. Compounds 3 and 4 exhibited inhibitory activity against Staphylococcus aureus with MIC values of 0.303 and 0.205 mM, respectively. The results indicated that these antimicrobial constituents of this crude drug might be responsible for its clinical antimicrobial effect. Molecules 2013-05-08 18 5 Article 10.3390/molecules18055265 5265 5287 1420-3049 2013-05-08 doi: 10.3390/molecules18055265 Shuo Xu Ming-Ying Shang Guang-Xue Liu Feng Xu Xuan Wang Cheng-Chao Shou Shao-Qing Cai http://www.mdpi.com/1420-3049/18/5/5251 We report the development of a new microwave-based synthetic methodology mediated by Woollins’ reagent that allowed an efficient conversion of caffeine into 6-selenocaffeine. A preliminary evaluation on the modulation of antioxidant activity upon selenation of caffeine, using the DPPH assay, indicated a mild antioxidant activity for 6-selenocaffeine, contrasting with caffeine, that exhibited no antioxidant activity under the same experimental conditions. Interestingly, whereas 6-selenocaffeine has revealed to have a low cytotoxic potential in both MCF10A and MCF-7 breast cells (24 h, up to 100 µM, MTT assay), a differential effect was observed when used in combination with the anticancer agents doxorubicin and oxaliplatin in MCF-7 breast cancer cells. The co-treatment of doxorubicin (1 µM) and 6-selenocaffeine (100 µM) resulted in a slight decrease in cellular viability when compared to doxorubicin (1 µM) alone. Conversely, the seleno-caffeine derivative at the same concentration markedly increased the viability of oxaliplatin (100 µM)-treated cells (p < 0.01). Overall, this work highlights an emerging methodology to synthesize organoselenium compounds and points out the differential roles of 6-selenocaffeine in the modulation of the cytotoxicity of anticancer agents. Molecules 2013-05-08 18 5 Article 10.3390/molecules18055251 5251 5264 1420-3049 2013-05-08 doi: 10.3390/molecules18055251 Inês Martins Joana Miranda Nuno Oliveira Ana Fernandes Sandrina Gonçalves Alexandra Antunes http://www.mdpi.com/1420-3049/18/5/5235 Two bisbenzylisoquinoline alkaloids, two morphine alkaloids, one aporphine alkaloid, syringaresinol and aristolochic acid І were selected as marker compounds and simultaneously analyzed using an ultra-high pressure liquid chromatography-diode array detection (UHPLC-DAD) method. These marker compounds were used for the quality control of Fangchi species of different origins, including Sinomenium acutum, Stephania tetrandra, Cocculus trilobus and Aristolochia fangchi. A reversed-phase UHPLC-DAD method was developed and validated for the simultaneous quantification of structurally diverse markers in different Fangchi species. In addition, an UHPLC-electrospray ionization tandem mass spectrometry (ESI-MS/MS) method was used for marker identification in Fangchi species, which provided diagnostic MS/MS spectral patterns that were dependent upon the marker structures. The UHPLC-MS/MS data were used to confirm and complement the UHPLC-DAD quality evaluation results. Additionally, magnoflorine and syringaresinol were observed for the first time in S. tetrandra and C. trilobus, respectively. Twenty different Fangchi species samples were analyzed for aristolochic acid I, syringaresinol and the alkaloids using the UHPLC-DAD and MS/MS method. Based on the levels of markers and principal component analysis (PCA), this method allowed for the clear classification of the samples into four different groups representing samples originating from the four species. Molecules 2013-05-07 18 5 Article 10.3390/molecules18055235 5235 5250 1420-3049 2013-05-07 doi: 10.3390/molecules18055235 Hee-Jung Sim Ji Kim Kang Lee Jongki Hong http://www.mdpi.com/1420-3049/18/5/5221 The aim of this work was to analyze the effect of sodium selenate fortification on the content of selenomethyl selenocysteine (SeMSC), total glucosinolates and sulforaphane, as well as the changes in protein profile of the inflorescences of broccoli (Brassica oleracea var. Italica). Two experimental groups were considered: plants treated with 100 mmol/L sodium selenate (final concentration in the pot) and control plants treated with water. Fortification began 2 weeks after transplantation and was repeated once a week during 10 weeks. Broccoli florets were harvested when they reached appropriate size. SeMSC content in broccoli florets increased significantly with sodium selenate fortification; but total glucosinolates and sulforaphane content as well as myrosinase activity were not affected. The protein profile of broccoli florets changed due to fortification with sodium selenate. Some proteins involved in general stress-responses were up-regulated, whereas down-regulated proteins were identified as proteins involved in protection against pathogens. This is the first attempt to evaluate the physiological effect of fortification with sodium selenate on broccoli at protein level. The results of this work will contribute to better understanding the metabolic processes related with selenium uptake and accumulation in broccoli. Molecules 2013-05-07 18 5 Article 10.3390/molecules18055221 5221 5234 1420-3049 2013-05-07 doi: 10.3390/molecules18055221 Ignacio Sepúlveda Herna Barrientos Andrea Mahn Alejandra Moenne http://www.mdpi.com/1420-3049/18/5/5209 We have theoretically analyzed the nuclear quantum effect on the nuclear magnetic shieldings for the intramolecular hydrogen-bonded systems of σ-hydroxy acyl aromatic species using the gauge-including atomic orbital technique combined with our multi-component density functional theory. The effect of H/D quantum nature for geometry and nuclear magnetic shielding changes are analyzed. Our study clearly demonstrated that the geometrical changes of hydrogen-bonds induced by H/D isotope effect (called geometrical isotope effect: GIE) is the dominant factor of deuterium isotope effect on 13C chemical shift. Molecules 2013-05-07 18 5 Article 10.3390/molecules18055209 5209 5220 1420-3049 2013-05-07 doi: 10.3390/molecules18055209 Taro Udagawa Takayoshi Ishimoto Masanori Tachikawa http://www.mdpi.com/1420-3049/18/5/5201 An asymmetric synthesis of 14-methyl-1-octadecene, the sex pheromone of the peach leafminer moth has been achieved. The target molecule was synthesized in six linear steps and in 30.3% overall yield from commercially available hexanoyl chloride, (S)-4-benzyloxazolidin-2-one and 1,9-nonanediol. The hexanoyl chloride was connected with (S)-4-benzyloxazolidin-2-one, and with the induction of the chiral oxazolidinone auxiliary, after chiral methylation, LAH reduction and then tosylation gave the chiral key intermediate 5 in high stereoselectivity. 1,9-Nonanediol, was selectively brominated, THP protected and subjected to Li2CuCl4-mediated C-C coupling to afford a C12 intermediate. The target molecule, (S)-14-methyl-1-octadecene, was obtained after the two parts were subjected to a second Li2CuCl4-mediated C-C coupling. Our synthetic approach represents the first time a substrate-control asymmetric synthesis of (S)-14-methyl-1-octadecene has been reported. Molecules 2013-05-07 18 5 Article 10.3390/molecules18055201 5201 5208 1420-3049 2013-05-07 doi: 10.3390/molecules18055201 Tao Zhang Wei-Li Ma Tian-Rui Li Jia Wu Jun-Run Wang Zhen-Ting Du http://www.mdpi.com/1420-3049/18/5/5190 Beyond other beneficial effects, a soy-rich diet has been shown to reduce the risk of cardiovascular diseases and diabetic complications. Reduction of oxidative and carbonyl stress has been proposed as the underlying mechanism, but the evidence for this is lacking. The aim of our study was to evaluate the effects of short-term increased soy intake on oxidative and carbonyl stress parameters in young volunteers. Young healthy probands (omnivores) of both genders (55 women, 33 men) were given soybeans (2 g/kg bodyweight daily) for one week. Markers of oxidative and carbonyl stress were measured in plasma at the beginning and at the end of one week soybean intake and after another week of a wash-out period. Total antioxidant capacity was increased by soybean intake in both genders. This led to decreased levels of advanced oxidation protein products in women, but not in men. On the contrary, in men, soybean intake increased lipoperoxidation. No effects on carbonyl stress markers (advanced glycation end products-specific fluorescence and fructosamine) were found. Soybean intake has gender-specific effects on oxidative stress in young healthy probands potentially due to divergent action and metabolism of phytoestrogens in men and women. Effects of soybean intake on carbonyl stress should be evaluated in longer studies. Molecules 2013-05-07 18 5 Article 10.3390/molecules18055190 5190 5200 1420-3049 2013-05-07 doi: 10.3390/molecules18055190 Peter Celec Július Hodosy Roland Pálffy Roman Gardlík Lukáč Halčák Daniela Ostatníková http://www.mdpi.com/1420-3049/18/5/5172 Phytochemical investigation of the n-BuOH-soluble fraction of the EtOH extract of the herbaceous stems of Ephedra sinica, which is known as Ephedrae Herba in Traditional Chinese Medicine, led to the isolation and identification of 12 A-type proanthocyanidins, containing five dimers, two trimers and five tetramers [i.e., (+)-epigallocatechin-(2α→O→7,4α→8)-(-)-catechin, named ephedrannin D1, a dimer; epigallocatechin-(2α→O→7,4α→8)-epigallocatechin-(4α→8)-catechin (ephedrannin Tr1), a trimer; and epigallocatechin-(2α→O→7,4α→8)-epigallocatechin-(4α→8)-epigallocatechin-(2α→O→7,4α→8)-gallocatechin, named ephedrannin Te1, a tetramer). Tetramers composed of gallocatechin are reported for the first time in Ephedraceae. Catechin, epicatechin, gallocatechin, epigallocatechin and four known dimers were also isolated. The structures were elucidated by extensive spectroscopic analysis. The absolute configurations of the 4α linkages, which were confirmed by NOESY and CD experiments, are the outstanding characteristic of most of these isolated A-type proanthocyanidins. The antimicrobial activities of these compounds were tested by measuring the minimum inhibitory concentrations (MIC) against bacteria (both Gram positive and Gram negative) and fungi, and were found to be in the range of 0.00515–1.38 mM. Compounds 6, 8, 10 and 11 exhibited moderate antimicrobial activities against Canidia albicans. Molecules 2013-05-06 18 5 Article 10.3390/molecules18055172 5172 5189 1420-3049 2013-05-06 doi: 10.3390/molecules18055172 Xinyu Zang Mingying Shang Feng Xu Jing Liang Xuan Wang Masayuki Mikage Shaoqing Cai http://www.mdpi.com/1420-3049/18/5/5163 To examine the effects of weak intermolecular interactions on solid-phase extraction (SPE) and chromatographic separation, we synthesized some novel stationary phases with a heavy atom effect layer by immobilizing halogenated aromatic rings and hydroxyl groups onto the surface of a hydrophilic base polymer. Using SPE cartridges packed with the functionalized materials, we found that the heavy atom stationary phases could selectively retain halophenols in organic solvents, such as 1-propanol which blocks the hydrogen bonding, or acetonitrile which blocks the p-p interaction. The extraction efficiency of the materials toward the halophenols depended on the dipole moments of phenoxy groups present as functional groups. On the other hand, the extraction efficiency of solutes toward the functional group depended on their molar refractions, i.e., induced dipole moments. The retention of the solutes to the stationary phase ultimately depended on not only strong intermolecular interactions, but also the effects of weak interactions such as the dispersion force. Molecules 2013-05-06 18 5 Article 10.3390/molecules18055163 5163 5171 1420-3049 2013-05-06 doi: 10.3390/molecules18055163 Toshio Miwa Atsushi Yamamoto Mitsuru Saito Yoshinori Inoue http://www.mdpi.com/1420-3049/18/5/5155 Cys-disulfide bonds contribute to the stabilization of peptide and protein structures. The synthesis of these molecules requires a proper protection of Cys residues, which is crucial to prevent side-reactions and also to achieve the correct Cys connectivity. Here we undertook a mechanistic study of a set of well-known acid-labile Cys protecting groups, as well other new promising groups, in order to better understand the nature of their acid-lability. The stability of the carbocation generated during the acid treatment was found to have a direct impact on the removal of the protective groups from the corresponding protected Cys-containing peptides. Hence a combination of steric and conjugative effects determines the stability of the carbocations generated. Here we propose diphenylmethyl (Dpm) as a promising protecting group on the basis of its intermediate relative carbocation stability. All the optimized geometries and energies presented in this study were determined using a B3LYP/6-31G(d,p) calculation. The results discussed herein may be of broader applicability for the development of new protecting groups. Molecules 2013-05-06 18 5 Article 10.3390/molecules18055155 5155 5162 1420-3049 2013-05-06 doi: 10.3390/molecules18055155 Iván Ramos-Tomillero Lorena Mendive-Tapia Miriam Góngora-Benítez Ernesto Nicolás Judit Tulla-Puche Fernando Albericio http://www.mdpi.com/1420-3049/18/5/5142 An efficient synthesis of novel dispirooxindoles has been achieved through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylideneimidazolidine-2,4-dione. The improved procedure features mild reaction conditions, high yields, high diastereoselectivities, a one-pot procedure and operational simplicity. Molecules 2013-05-03 18 5 Article 10.3390/molecules18055142 5142 5154 1420-3049 2013-05-03 doi: 10.3390/molecules18055142 Jun He Guang Ouyang Zhixiang Yuan Rongsheng Tong Jianyou Shi Liang Ouyang http://www.mdpi.com/1420-3049/18/5/5125 Herb-herb combinations have been used in Chinese medicine practice for thousands of years, yet scientific evidence of their therapeutic benefits is lacking. With increasing interest in shifting from the one-drug-one-target paradigm to combination therapy or polypharmacy to achieve therapeutic benefits for a number of diseases, there is momentum to explore new knowledge by tapping the past empirical experiences of herb-herb combinations. This review presents an overview of the traditional concept and practice of herb-herb combination in Chinese medicine, and highlights the available scientific and clinical evidence to support the combined use of herbs. It is hoped that such information would provide a lead for developing new approaches for future therapeutic advancement and pharmaceutical product development. Very likely modern technologies combined with innovative research for the quality control of herbal products, identification of active components and understanding of the molecular mechanism, followed by well-designed animal and clinical studies would pave the way in advancing the wealth of empirical knowledge from herb-herb combination to new therapeutic modalities. Molecules 2013-05-03 18 5 Review 10.3390/molecules18055125 5125 5141 1420-3049 2013-05-03 doi: 10.3390/molecules18055125 Chun-Tao Che Zhi Wang Moses Chow Christopher Lam http://www.mdpi.com/1420-3049/18/5/5104 The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent. Molecules 2013-05-02 18 5 Article 10.3390/molecules18055104 5104 5124 1420-3049 2013-05-02 doi: 10.3390/molecules18055104 Andrijana Meščić Svjetlana Krištafor Ivana Novaković Amar Osmanović Ursina Müller Davorka Završnik Simon Ametamey Leonardo Scapozza Silvana Raić-Malić http://www.mdpi.com/1420-3049/18/5/5091 Photochromic diarylethenes (DAEs) are among the most promising molecular switching systems for future molecular electronics. Numerous derivatives have been synthesized recently, and experimental quantum yields (QYs) have been reported for two categories of them. Although the QY is one of the most important properties in various applications, it is also the most difficult property to predict before a molecule is actually synthesized. We have previously reported preliminary theoretical studies on what determines the QYs in both categories of DAE derivatives. Here, reflecting theoretical analyses of potential energy surfaces and recent experimental results, a rational explanation of the general guiding principle for QY design is presented for future molecular design. Molecules 2013-05-02 18 5 Review 10.3390/molecules18055091 5091 5103 1420-3049 2013-05-02 doi: 10.3390/molecules18055091 Shinichiro Nakamura Kingo Uchida Makoto Hatakeyama http://www.mdpi.com/1420-3049/18/5/5072 Phenolic compounds are abundant secondary metabolites in plums, with potential health benefits believed to be due to their antioxidant activity, amongst others. Phenolic characterisation of South African Prunus salicina Lindl. plums is necessary to fully evaluate their potential health benefits. An HPLC method using diode-array detection (DAD) for quantification of phenolic compounds was improved and fluorescence detection (FLD) was added for quantification of flavan-3-ols. Validation of the HPLC-DAD-FLD method showed its suitability for quantification of 18 phenolic compounds, including flavan-3-ols using FLD, and phenolic acids, anthocyanins and flavonols using DAD. The method was suitable for characterisation of the phenolic composition of 11 South African plum cultivars and selections, including various types with yellow and red skin and flesh. The method was used in conjunction with mass spectrometry (MS) to identify 24 phenolic compounds. Neochlorogenic acid and cyanidin-3-O-glucoside were the major compounds in most of the plums, while cyanidin-3-O-glucoside was absent in Sun Breeze plums with yellow skin and flesh. Post-column on-line coupling of the ABTS•+ scavenging assay with HPLC-DAD enabled qualitative evaluation of the relative contribution of individual phenolic compounds to the antioxidant activity. The flavan-3-ols, neochlorogenic acid and cyanidin-3-O-glucoside displayed the largest antioxidant response peaks. Molecules 2013-05-02 18 5 Article 10.3390/molecules18055072 5072 5090 1420-3049 2013-05-02 doi: 10.3390/molecules18055072 Alet Venter Elizabeth Joubert Dalene de Beer http://www.mdpi.com/1420-3049/18/5/5059 A series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein VP1. The preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against EV71 and Coxsackievirus A16 with low cytotoxicity. Molecules 2013-04-29 18 5 Article 10.3390/molecules18055059 5059 5071 1420-3049 2013-04-29 doi: 10.3390/molecules18055059 Xian Zhang Hongliang Wang Yuhuan Li Ruiyuan Cao Wu Zhong Zhibing Zheng Gang Wang Junhai Xiao Song Li http://www.mdpi.com/1420-3049/18/5/5051 Two new sesquiterpenoids, (−)-(1S*,2S*,3R*)-3-ethoxycupar-5-ene-1,2-diol (1) and (−)-(1S*,4S*,9S*)-1,9-epoxybisabola-2,10-diene-4-ol (2), along with six known compounds 3−8, were isolated from the EtOH extract of the herb of Leonurus japonicus. Their structures were elucidated by physical and spectroscopic analysis. In the in vitro assays, compounds 7 and 8 showed obvious antibacterial activity against several bacteria strains, while compound 3 significantly inhibited abnormal increase of platelet aggregation induced by ADP. Molecules 2013-04-29 18 5 Article 10.3390/molecules18055051 5051 5058 1420-3049 2013-04-29 doi: 10.3390/molecules18055051 Liang Xiong Qin-Mei Zhou Cheng Peng Xiao-Fang Xie Li Guo Xiao-Hong Li Juan Liu Zhao-Hua Liu Ou Dai http://www.mdpi.com/1420-3049/18/5/5032 Quantitative structure–activity relationship (QSAR) studies were performed in order to identify molecular features responsible for the antileishmanial activity of 61 adenosine analogues acting as inhibitors of the enzyme glyceraldehyde 3-phosphate dehydrogenase of Leishmania mexicana (LmGAPDH). Density functional theory (DFT) was employed to calculate quantum-chemical descriptors, while several structural descriptors were generated with Dragon 5.4. Variable selection was undertaken with the ordered predictor selection (OPS) algorithm, which provided a set with the most relevant descriptors to perform PLS, PCR and MLR regressions. Reliable and predictive models were obtained, as attested by their high correlation coefficients, as well as the agreement between predicted and experimental values for an external test set. Additional validation procedures were carried out, demonstrating that robust models were developed, providing helpful tools for the optimization of the antileishmanial activity of adenosine compounds. Molecules 2013-04-29 18 5 Article 10.3390/molecules18055032 5032 5050 1420-3049 2013-04-29 doi: 10.3390/molecules18055032 Norka Lozano Rafael Oliveira Karen Weber Kathia Honorio Rafael Guido Adriano Andricopulo Albérico Silva http://www.mdpi.com/1420-3049/18/5/5005 The folate receptor (FR) is expressed in many tumor types, among those ovarian and lung cancer. Due to the high FR affinity of folic acid, it has been used for targeting of FR-positive tumors, allowing specific delivery of attached probes to the malignant tissue. Therefore, nuclear imaging of FR-positive cancer is of clinical interest for selecting patients who could benefit from innovative therapy concepts based on FR-targeting. Positron emission computed tomography (PET) has become an established technique in clinical routine because it provides an increased spatial resolution and higher sensitivity compared to single photon emission computed tomography (SPECT). Therefore, it is of critical importance to develop folate radiotracers suitable for PET imaging. This review article updates on the design, preparation and pre-clinical investigation of folate derivatives for radiolabeling with radioisotopes for PET. Among those the most relevant radionuclides so far are fluorine-18 (t1/2: 110 min, Eavβ+: 250 keV) and gallium-68 (t1/2: 68 min, Eav β+: 830 keV). Recent results obtained with new PET isotopes such as terbium-152 (t1/2: 17.5 h, Eβ+: 470 keV) or scandium-44 (t1/2: 3.97 h, Eav β+: 632 keV) are also presented and discussed. Current endeavors for clinical implementation of PET agents open new perspectives for identification of FR-positive malignancies in patients. Molecules 2013-04-29 18 5 Review 10.3390/molecules18055005 5005 5031 1420-3049 2013-04-29 doi: 10.3390/molecules18055005 Cristina Müller http://www.mdpi.com/1420-3049/18/5/4986 Amino acid ionic liquid-supported Schiff bases, derivatives of salicylaldehyde and various amino acids (L-threonine, L-valine, L-leucine, L-isoleucine and L-histidine) have been investigated by means of various spectroscopic techniques (NMR, UV-Vis, IR, MS) and deuterium isotope effects on 13C-NMR chemical shifts. The results have shown that in all studied amino acid ionic liquid-supported Schiff bases (except the L-histidine derivative) a proton transfer equilibrium exists and the presence of the COO− group stabilizes the proton transferred NH-form. Molecules 2013-04-29 18 5 Article 10.3390/molecules18054986 4986 5004 1420-3049 2013-04-29 doi: 10.3390/molecules18054986 Paula Ossowicz Ewa Janus Grzegorz Schroeder Zbigniew Rozwadowski http://www.mdpi.com/1420-3049/18/5/4972 The crystal structure of a naturally occurring cyclic tetrapeptide cyclo(Gly-L-Ser-L-Pro-L-Glu) [cyclo(GSPE)] was obtained. The conformation of synthesized cyclo(GSPE) fixes the coordination to lead ion in a 1:1 ratio. This cyclo(GSPE)-Pb complex was constructed as an asymmetric 3D network in the crystalline state. The polymerization of a heavy metal ion with a rigid asymmetric cyclic tetrapeptide represents the first example of a new class of macrocyclic complexes. Molecules 2013-04-26 18 5 Article 10.3390/molecules18054972 4972 4985 1420-3049 2013-04-26 doi: 10.3390/molecules18054972 Subrata Chakraborty Pooja Tyagi Dar-Fu Tai Gene-Hsiang Lee Shie-Ming Peng http://www.mdpi.com/1420-3049/18/5/4955 Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used against HIV-1. Currently, NVP is the most widely used anti-HIV drug in developing countries, both in combination therapy and to prevent mother-to-child transmission of HIV. Despite its efficacy against HIV, NVP produces a variety of toxic responses, including hepatotoxicity and skin rash. It is also associated with increased incidences of hepatoneoplasias in rodents. In addition, epidemiological data suggest that NNRTI use is a risk factor for non-AIDS-defining cancers in HIV-positive patients. Current evidence supports the involvement of metabolic activation to reactive electrophiles in NVP toxicity. NVP metabolism includes oxidation to 12-hydroxy-NVP; subsequent Phase II sulfonation produces an electrophilic metabolite, 12-sulfoxy-NVP, capable of reacting with DNA to yield covalent adducts. Since 2’-deoxythymidine (dT) adducts from several alkylating agents are regarded as having significant mutagenic/carcinogenic potential, we investigated the formation of NVP-dT adducts under biomimetic conditions. Toward this goal, we initially prepared and characterized synthetic NVP-dT adduct standards using a palladium-mediated Buchwald-Hartwig coupling strategy. The synthetic standards enabled the identification, by LC-ESI-MS, of 12-(2'-deoxythymidin-N3-yl)-nevirapine (N3-NVP-dT) in the enzymatic hydrolysate of salmon testis DNA reacted with 12-mesyloxy-NVP, a synthetic surrogate for 12-sulfoxy-NVP. N3-NVP-dT, a potentially cytotoxic and mutagenic DNA lesion, was also the only dT-specific adduct detected upon reaction of dT with 12-mesyloxy-NVP. Our data suggest that N3-NVP-dT may be formed in vivo and play a role in the hepatotoxicity and/or putative hepatocarcinogenicity of NVP. Molecules 2013-04-26 18 5 Article 10.3390/molecules18054955 4955 4971 1420-3049 2013-04-26 doi: 10.3390/molecules18054955 Alexandra Antunes Benjamin Wolf M. Oliveira Frederick Beland M. Marques http://www.mdpi.com/1420-3049/18/5/4942 The methanol extracts of leaf skins and flowers of Aloe vera from the Canary Islands were analyzed for their phenolic profiles and screened for their antioxidant and antimycoplasmic activities. The use of reversed phase high performance liquid chromatography (RP-HPLC) allowed the identification of 18 phenolic constituents. Leaf skin extracts were characterized by the abundance of catechin, sinapic acid and quercitrin. Gentisic acid, epicatechin and quercitrin were the most prominent phenolic compounds of the flowers. The in vitro antioxidant activities determined by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric antioxidant reducing power (FRAP) assays revealed that both extracts exhibited antioxidant activity, being the leaf skin extract the most active fraction. The leaf skin extract was also found to be active against the microbial strains tested. Therefore, A. vera extracts from leaf skin and flowers can be considered as good natural antioxidant sources. Molecules 2013-04-26 18 5 Article 10.3390/molecules18054942 4942 4954 1420-3049 2013-04-26 doi: 10.3390/molecules18054942 Aroa López Miguel de Tangil Orestes Vega-Orellana Ana Ramírez Milagros Rico http://www.mdpi.com/1420-3049/18/5/4929 Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer’s disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau229-237[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B241-255 originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible. Molecules 2013-04-26 18 5 Article 10.3390/molecules18054929 4929 4941 1420-3049 2013-04-26 doi: 10.3390/molecules18054929 Karla Ramírez-Gualito Monique Richter Manolis Matzapetakis David Singer Stefan Berger http://www.mdpi.com/1420-3049/18/5/4917 Non-thermal plasmas are emerging as a novel tool for the treatment of living tissues for biological and medical purpose. In this study, we described the effect of 4 min dielectric barrier discharge (DBD) plasma on both T98G cancer and HEK normal cell lines in the presence of different concentrations of osmolytes. This treatment strategy shows a specific inhibitory effect of a 240 s plasma exposure in the presence of osmolytes against T98G brain cancer cells only, but not on HEK normal cells. Based on these interesting properties of osmolytes, a non-thermal plasma appears to be a potential anticancer treatment strategy for different kinds of cancers in the presence of osmolytes. Molecules 2013-04-25 18 5 Article 10.3390/molecules18054917 4917 4928 1420-3049 2013-04-25 doi: 10.3390/molecules18054917 Nagendra Kaushik Pankaj Attri Neha Kaushik Eun Choi http://www.mdpi.com/1420-3049/18/5/4906 Zero-point vibrational level averaging for electron spin resonance (ESR) and muon spin resonance (µSR) hyperfine coupling constants (HFCCs) are computed for H and Mu isotopomers of the cyclohexadienyl radical. A local mode approximation previously developed for computation of the effect of replacement of H by D on 13C-NMR chemical shifts is used. DFT methods are used to compute the change in energy and HFCCs when the geometry is changed from the equilibrium values for the stretch and both bend degrees of freedom. This variation is then averaged over the probability distribution for each degree of freedom. The method is tested using data for the methylene group of C6H7, cyclohexadienyl radical and its Mu analog. Good agreement is found for the difference between the HFCCs for Mu and H of CHMu and that for H of CHMu and CH2 of the parent radical methylene group. All three of these HFCCs are the same in the absence of the zero point average, a one-parameter fit of the static HFCC, a(0), can be computed. That value, 45.2 Gauss, is compared to the results of several fixed geometry electronic structure computations. The HFCC values for the ortho, meta and para H atoms are then discussed. Molecules 2013-04-25 18 5 Article 10.3390/molecules18054906 4906 4916 1420-3049 2013-04-25 doi: 10.3390/molecules18054906 Bruce Hudson Suzanne Chafetz http://www.mdpi.com/1420-3049/18/5/4887 Attempts to relate sensory analysis data to specific chemicals such as volatile compounds have been frequent. Often these associations are difficult to interpret or are weak in nature. Although some difficulties may relate to the methods used, the difficulties also result from the complex nature of flavor. For example, there are multiple volatiles responsible for a flavor sensation, combinations of volatiles yield different flavors than those expected from individual compounds, and the differences in perception of volatiles in different matrices. This review identifies some of the reasons sensory analysis and instrumental measurements result in poor associations and suggests issues that need to be addressed in future research for better understanding of the relationships of flavor/aroma phenomena and chemical composition. Molecules 2013-04-25 18 5 Review 10.3390/molecules18054887 4887 4905 1420-3049 2013-04-25 doi: 10.3390/molecules18054887 Edgar IV Kadri Koppel http://www.mdpi.com/1420-3049/18/5/4876 Fifteen phenolic compounds, including three caffeoyl derivatives, four gallotannins, three ellagitannins and five flavonoids, were isolated from an 80% MeOH extract of the leaves of Corylopsis coreana Uyeki (Korean winter hazel; CL). The anti-oxidative activities [1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT)] and the anti-proliferative activity on human prostate cancer cell lines (DU145 and LNCaP) were also evaluated. Molecules 2013-04-24 18 5 Article 10.3390/molecules18054876 4876 4886 1420-3049 2013-04-24 doi: 10.3390/molecules18054876 Manh Kim Sung Ha Myeong Oh Han Kim So Kim Min Lee http://www.mdpi.com/1420-3049/18/5/4868 Four triterpenes were isolated from a traditional Japanese tea product produced by anaerobic microbial fermentation of heated green tea leaves (Camellia sinensis). Two of the compounds were novel and characterized by spectroscopic investigation to be 13,26-epoxy-3β,11α-dihydroxyolean-12-one and 3β,11α,13β-trihydroxyolean-12-one. Two known triterpenes were identified as taraxastane-3β,20β-diol and taraxastane-3β,20α-diol. These triterpenes were not detected in the original green tea leaves. Molecules 2013-04-24 18 5 Article 10.3390/molecules18054868 4868 4875 1420-3049 2013-04-24 doi: 10.3390/molecules18054868 Yong-Lin Huang Sachi Nagai Takashi Tanaka Yosuke Matsuo Yoshinori Saito Isao Kouno http://www.mdpi.com/1420-3049/18/5/4858 Little is known about the efficacy of pulsed ultrasound compared with continuous ultrasound. Previous studies on the efficacy of pulsed ultrasound were not systematic and gave different results. In this study, the effects of pulse length, pulse interval, pulse length × pulse intervals, and treatment time on sonochemical activity were investigated using a simple oxidation of iodide method and a comparison of the efficacy of pulsed ultrasound and continuous ultrasound is made. The results showed that the main factor in the efficacy of pulsed ultrasound was pulse length when pulse length varied from 0.1 to 1 s. However, the main factors were pulse length, the pulse length × pulse interval, and pulse interval when pulse length varied from 1 to 9 s. Pulsed ultrasound had no effect when the pulse length was 0.1 s; however, the sonochemical activity of pulsed ultrasound decreased compared to continuous ultrasound as the pulse length varied from 0.1 to 1 s. The sonochemical activity of pulsed ultrasound either increased or decreased compared to continuous ultrasound when pulse length varied from 1 to 9 s, but the increase or decrease had no clear trend. The sonochemical activity was constant at Ton/Toff = 2 s/2 s and slightly decreased at Ton/Toff = 3 s/2 s with time, whereas the sonochemical activity of continuous ultrasound significantly decreased with time. Enhancement or reduction of sonochemical activity of pulsed ultrasound compared to continuous ultrasound depended on the pulse length and pulse interval. Molecules 2013-04-24 18 5 Article 10.3390/molecules18054858 4858 4867 1420-3049 2013-04-24 doi: 10.3390/molecules18054858 Yujing Sun Xingqian Ye http://www.mdpi.com/1420-3049/18/5/4844 Metabolomics, the latest of the “omics” sciences, has a non-selective approach and can thus lead to the identification of all the metabolites (molecules < 1 kDa) in a biological system. The metabolomic profile can be considered the most predictive phenotype capable of evaluating epigenetic modifications determined by external factors. It is so close to the phenotype as to be considered the phenotype itself in its unique individuality (fingerprinting), both in health (phenome), and disease (diseasome). Urine, compared to other biological liquids, has the advantage of being a complex fluid with many components, including intermediate metabolites. Metabolomics may thus play a role in the study of different kidney diseases and overcome diagnostic difficulties. We shall present the studies that to our knowledge have been published on Nephrology and Pediatric Nephrology. Some are experimental while others are clinical. We have not considered carcinomas and transplantations. Although scarce, the data on adults and the very few ones in pediatrics are quite interesting. Further studies on kidneys are needed to determine the practical clinical impact of metabolomics in kidney renal pathologies. The “multiplatform” “omic” study of urine and namely metabolomics can contribute to improving early diagnosis and the outcome of kidney diseases. Molecules 2013-04-24 18 5 Review 10.3390/molecules18054844 4844 4857 1420-3049 2013-04-24 doi: 10.3390/molecules18054844 Vassilios Fanos Claudia Fanni Giovanni Ottonello Antonio Noto Angelica Dessì Michele Mussap http://www.mdpi.com/1420-3049/18/4/4816 Factors affecting the kinetic isotope effects (KIEs) of the gas-phase SN2 reactions and their temperature dependence have been analyzed using the ion-molecule collision theory and the transition state theory (TST). The quantum-mechanical tunneling effects were also considered using the canonical variational theory with small curvature tunneling (CVT/SCT). We have benchmarked a few ab initio and density functional theory (DFT) methods for their performance in predicting the deuterium KIEs against eleven experimental values. The results showed that the MP2/aug-cc-pVDZ method gave the most accurate prediction overall. The slight inverse deuterium KIEs usually observed for the gas-phase SN2 reactions at room temperature were due to the balance of the normal rotational contribution and the significant inverse vibrational contribution. Since the vibrational contribution is a sensitive function of temperature while the rotation contribution is temperature independent, the KIEs are thus also temperature dependent. For SN2 reactions with appreciable barrier heights, the tunneling effects were predicted to contribute significantly both to the rate constants and to the carbon-13, and carbon-14 KIEs, which suggested important carbon atom tunneling at and below room temperature. Molecules 2013-04-23 18 4 Article 10.3390/molecules18044816 4816 4843 1420-3049 2013-04-23 doi: 10.3390/molecules18044816 Wan-Chen Tsai Wei-Ping Hu http://www.mdpi.com/1420-3049/18/4/4803 The intravenous (IV) and subcutaneous (SC) toxicity and absorption kinetics of the antileishmanial triterpene saponin PX-6518 and its active constituents maesabalide-III and -IV were studied in mice and dogs. A high-dose wash-out study of PX-6518 at 20 mg/kg SC for 5 days and a single low-dose wash-out study at 1, 2.5 or 5 mg/kg SC and IV with follow-up until day 35 after treatment were performed in mice. Beagle dogs received three escalating doses of maesabalide-III and -IV at weekly intervals (0.01, 0.1 and 0.5 mg/kg IV and maesabalide-III was also dosed SC at 0.1, 0.2 and 0.4 mg/kg). Endpoint measurements included clinical, hematological and serum biochemical parameters. Pathology and toxicokinetic studies were performed on the dogs. Whereas the neutrophils and aspartate aminotransferase and alanine aminotransferase levels were increased in the high-dose wash-out mouse study, these parameters did not change in the low-dose wash-out study. The dogs were far more susceptible than mice to liver toxicity (hepatocellular necrosis and elevated liver enzymes) and developed a painful inflammatory reaction at the SC injection site. Toxicokinetic analysis revealed a non dose-linear systemic availability with plasma concentrations above the antileishmanial IC50 after only a single dose at 0.01 mg/kg IV or 0.1 mg/kg SC. Related to the long half-life (T1/2 71–91 h after SC dosing), repeated dosing at weekly intervals may result in drug accumulation and enhanced toxicity. It was decided not to pursue further drug development for PX-6518 because of the hepatotoxic risk. Molecules 2013-04-22 18 4 Article 10.3390/molecules18044803 4803 4815 1420-3049 2013-04-22 doi: 10.3390/molecules18044803 Louis Maes http://www.mdpi.com/1420-3049/18/4/4786 Chemical shifts (CS) of the 1H nucleus in N···H···O type hydrogen bonds (H-bond) were observed in some complexes between chlorophenols [pentachlorophenol (PCP), 2,4,6-tricholorophenol (TCP), 2,6-dichlorophenol (26DCP), 3,5-dichlorophenol (35DCP), and p-chlorophenol (pCP)] and nitrogen-base (N-Base) by solid-state high-resolution 1H-NMR with the magic-angle-spinning (MAS) method. Employing N-Bases with a wide range of pKa values (0.65–10.75), 1H-MAS-NMR CS values of bridging H atoms in H-bonds were obtained as a function of the N-Base’s pKa. The result showed that the CS values were increased with increasing pKa values in a range of DpKa < 0 [DpKa = pKa(N-Base) - pKa(chlorophenols)] and decreased when DpKa > 2: The maximum CS values was recorded in the PCP (pKa = 5.26)–4-methylpyridine (6.03), TCP (6.59)–imidazole (6.99), 26DCP (7.02)–2-amino-4-methylpyridine (7.38), 35DCP (8.04)–4-dimethylaminopyridine (9.61), and pCP (9.47)–4-dimethylaminopyridine (9.61) complexes. The largest CS value of 18.6 ppm was recorded in TCP–imidazole crystals. In addition, H/D isotope effects on 1H-MAS-NMR spectra were observed in PCP–2-amino-3-methylpyridine. Based on the results of CS simulation using a B3LYP/6-311+G** function, it can be explained that a little changes of the N–H length in H-bond contribute to the H/D isotope shift of the 1H-MAS-NMR peaks. Molecules 2013-04-22 18 4 Article 10.3390/molecules18044786 4786 4802 1420-3049 2013-04-22 doi: 10.3390/molecules18044786 Hisashi Honda http://www.mdpi.com/1420-3049/18/4/4776 The vibrational dispersion relations of porous germanium (pGe) and germanium nanowires (GeNWs) were calculated using the ab initio density functional perturbation theory with a generalized gradient approximation with norm-conserving pseudopotentials. Both pores and nanowires were modeled using the supercell technique. All of the surface dangling bonds were saturated with hydrogen atoms. To address the difference in the confinement between the pores and the nanowires, we calculated the vibrational density of states of the two materials. The results indicate that there is a slight shift in the highest optical mode of the Ge-Ge vibration interval in all of the nanostructures due to the phonon confinement effects. The GeNWs exhibit a reduced phonon confinement compared with the porous Ge due to the mixed Ge-dihydride vibrational modes around the maximum bulk Ge optical mode of approximately 300 cm−1; however, the general effects of such confinements could still be noticed, such as the shift to lower frequencies of the highest optical mode belonging to the Ge vibrations. Molecules 2013-04-22 18 4 Article 10.3390/molecules18044776 4776 4785 1420-3049 2013-04-22 doi: 10.3390/molecules18044776 Alejandro Trejo Miguel Cruz-Irisson http://www.mdpi.com/1420-3049/18/4/4766 Two new compounds, ethylconiferin (1) and (−)-lariciresinol 4-(6'''-O-cinnamyl-β-d-glucopyranoside) (2), along with the three known compounds (+)-pinoresinol (3), (+)-cycloolivil (4), nobiletin (5), were isolated from the root of Jasminum girialdii. All these compounds were isolated for the first time from this source. Their structures were elucidated on the basis of extensive spectroscopic analysis and chemical methods. In addition, the in vitro cytotoxic activity of these compounds was evaluated. The results showed that none of the compounds had any significant inhibitory activities on the proliferation of HCT-116 and SW-620 cells. Molecules 2013-04-22 18 4 Article 10.3390/molecules18044766 4766 4775 1420-3049 2013-04-22 doi: 10.3390/molecules18044766 Zhenggang Yue Hui Qin Yuhua Li Yang Sun Zhipeng Wang Tiehong Yang Li Liu Minchang Wang Feng Feng Qibing Mei http://www.mdpi.com/1420-3049/18/4/4739 The application of the Suzuki-Miyaura reaction in the synthesis of flavonoids, an important class of natural products, is reviewed. This reaction has not only been employed to provide access to flavonoid nuclei, but has also been applied to the synthesis of dimeric flavonoids and in the synthesis of libraries of flavonoid derivatives for biological activity studies. The classes of flavonoids that are discussed are the chalcones, flavones, isoflavones, neoflavones, biflavones and derivatives of flavonoids obtained by C-C bond formation via the Suzuki-Miyaura reaction. Molecules 2013-04-22 18 4 Review 10.3390/molecules18044739 4739 4765 1420-3049 2013-04-22 doi: 10.3390/molecules18044739 Mamoalosi Selepe Fanie Van Heerden http://www.mdpi.com/1420-3049/18/4/4728 The tridentate ligand 2,6-bis(3,5-diphenylpyrazol-1-ylmethyl)pyridine, abbreviated as 2,6-[(3,5-ph2pz-CH2)2-py], a new pyridine-pyrazole derivative, was prepared from 2,6-bis(bromomethyl)pyridine and 3,5-diphenylpyrazole. The ligand was characterized by means of elemental analyses, ATR-IR, 1H- and 13C-NMR spectroscopy and single crystal X-ray crystallography. Using this ligand, a new mononuclear vanadium (III) complex, {2,6-[(3,5-ph2pz)CH2]2py}VCl3 was prepared and characterized by elemental analysis, ATR-IR and HR-MS. The complex was investigated as a catalyst for ethylene polymerization and compared with 2,6-[(3,5-Me2pz)CH2]2py}VCl3 to explore the effect of the substituent on the pyrazolyl rings on ethylene polymerization. High catalytic activity was observed at ambient temperature. After treatment with AlEtCl2, these complexes showed high activity for ethylene polymerization converting ethylene to highly linear polyethylene and affording high molecular weight polymers (up to 1.0 × 106 g/mol) with unimodal molecular weight distributions. Molecules 2013-04-22 18 4 Article 10.3390/molecules18044728 4728 4738 1420-3049 2013-04-22 doi: 10.3390/molecules18044728 Hanna Abbo Salam Titinchi http://www.mdpi.com/1420-3049/18/4/4718 Malaria and leishmaniasis are two of the World’s most important tropical parasitic diseases. Continuing with our efforts to identify new compounds active against malaria and leishmaniasis, twelve new 1,4-di-N-oxide quinoxaline derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum FCR-3 strain, Leishmania infantum and Leishmania amazonensis. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. The results obtained indicate that a cyclopentyl derivative had the best antiplasmodial activity (2.9 µM), while a cyclohexyl derivative (2.5 µM) showed the best activity against L. amazonensis, and a 3-chloropropyl derivative (0.7 µM) showed the best results against L. infantum. All these compounds also have a Cl substituent in the R7 position. Molecules 2013-04-22 18 4 Article 10.3390/molecules18044718 4718 4727 1420-3049 2013-04-22 doi: 10.3390/molecules18044718 Carlos Barea Adriana Pabón Silvia Pérez-Silanes Silvia Galiano German Gonzalez Antonio Monge Eric Deharo Ignacio Aldana http://www.mdpi.com/1420-3049/18/4/4703 Nowadays, chemically synthesized proteins and peptides are attractive building blocks and have potential in many important applications as biomaterials. In this review, applications of biomaterials to thermotropic liquid crystals are discussed. The review covers the improvement of the performance of liquid crystal displays using liquid crystal physical gels consisting of a liquid crystal and amino acid-based gelators, and also new functionalization of liquid crystals. Moreover, the influence of DNA, which is one of the more attractive biomaterials, dispersed in thermotropic liquid crystals and its potential use in the liquid crystal industry is described. In addition, we found interesting results during electrooptical measurements of liquid crystals doped with DNA, and explain them from the point of view of biological applications. These recent approaches suggest that these biomaterials may be applicable in the electronic device industry and should be considered as an interesting material with their physical properties having the potential to create or refine an industrial product. Molecules 2013-04-19 18 4 Review 10.3390/molecules18044703 4703 4717 1420-3049 2013-04-19 doi: 10.3390/molecules18044703 Kazuki Iwabata Urara Sugai Yasutaka Seki Hirokazu Furue Kengo Sakaguchi http://www.mdpi.com/1420-3049/18/4/4689 Resveratrol (RES) is a well-known phytocompound and food component which has antioxidative and multifunctional bioactivities. However, there is limited evidence for the effects of RES on physical fatigue and exercise performance. The purpose of this study was to evaluate the potential beneficial effects of trans-RES on fatigue and ergogenic functions following physiological challenge. Male ICR mice from four groups (n = 8 per group) were orally administered RES for 21 days at 0, 25, 50, and 125 mg/kg/day, which were respectively designated the vehicle, RES-25, RES-50, and RES-125 groups. The anti-fatigue activity and exercise performance were evaluated using forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after a 15-min swimming exercise. The exhaustive swimming time of the RES-25 group (24.72 ± 7.35 min) was significantly (p = 0.0179) longer than that of vehicle group (10.83 ± 1.15 min). A trend analysis revealed that RES treatments increased the grip strength. RES supplementation also produced dose-dependent decreases in serum lactate and ammonia levels and CK activity and also an increase in glucose levels in dose-dependent manners after the 15-min swimming test. The mechanism was related to the increased energy utilization (as blood glucose), and decreased serum levels of lactate, ammonia, and CK. Therefore, RES could be a potential agent with an anti-fatigue pharmacological effect. Molecules 2013-04-19 18 4 Article 10.3390/molecules18044689 4689 4702 1420-3049 2013-04-19 doi: 10.3390/molecules18044689 Ruei-Er Wu Wen-Ching Huang Chen-Chung Liao Yu-Kai Chang Nai-Wen Kan Chi-Chang Huang http://www.mdpi.com/1420-3049/18/4/4679 New aryl-hydrazinyl-1,3-selenazole and aroyl-hydrazonyl-1,3-selenazoles were synthesized via Hantzsch type condensation reactions of selenosemicarbazides with α-halogenocarbonyl derivatives, under classical versus microwave heating conditions. Excellent yields and shorter reaction times were obtained under irradiation conditions. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR, 1H-NMR), MS and elemental analysis. Selenazole derivatives were screened for their anti-proliferative effects against two leukemia cell lines (CCRF-CEM and HL60) and three carcinoma cell lines (MDA-MB231, HCT116 and U87MG). Molecules 2013-04-19 18 4 Article 10.3390/molecules18044679 4679 4688 1420-3049 2013-04-19 doi: 10.3390/molecules18044679 Adriana (Grozav) Luiza Gaina Victor Kuete Luminita Silaghi-Dumitrescu Thomas Efferth Valentin Zaharia http://www.mdpi.com/1420-3049/18/4/4669 A series of thieno[2,3-b]thiophene moiety-containing bis-cyanopyrazoles 5a–c, bis-aminopyrazole 9 and bis-pyridazine derivatives 11 were synthesized and evaluated in vitro for their antimicrobial potential. The antimicrobial activity of some selected products was evaluated and showed good results. 5,5'-(3,4-Dimethylthieno[2,3-b]thiophene-2,5-diyl)bis(3-acetyl-1-(4-chlorophenyl)-1H-pyrazole-4-carbonitrile) (5d) was found to be more potent than the standard drug amphotericin B against Geotricum candidum and equipotent to amphotericin B against Syncephalastrum racemosum. In addition, it was found to be equipotent to the standard drug Penicillin G against Staphylococcus aureus. Moreover, it was more potent than the standard drug streptomycin against Pseudomonas aeruginosa and Escherichia coli. Molecules 2013-04-19 18 4 Article 10.3390/molecules18044669 4669 4678 1420-3049 2013-04-19 doi: 10.3390/molecules18044669 Yahia Mabkhot Nabila Kheder Ahmad Farag http://www.mdpi.com/1420-3049/18/4/4651 The present investigation has been carried out to investigate the biological role of four different types of baby-leaf salads and to study their potential as natural sources of antioxidants and antimicrobials against several isolates from important human pathogenic bacteria. Four single types of salads (green lettuce, red lettuce, rucola and watercress) and two mixtures [(1) red lettuce+green lettuce; (2) green lettuce + red lettuce + watercress + rucola] were assayed. The HPLC analysis revealed interesting levels of polyphenols and glucosinolates. The results showed a significant variation (p < 0.05) of polyphenols and glucosinolates with plant material. Nine different types of polyphenols grouped in three major classes were found: gallic acid, chlorogenic acid, caffeic acid and dicaffeoyltartaric acid (phenolic acids); quercitin-3-O-rutinoside, quercitin-3-O-rhamnoside, luteolin-7-O-glucoside and isorhamnetin (flavonoids); and cyanidin-3-glucoside (anthocyanins). Only three different glucosinolates were found: glucoraphanin; gluconasturtiin and 4-methoxy-glucobrassicin. A positive correlation was detected between polyphenol contents and antioxidant activity. Red lettuce and mixture 1 were the baby-leaf salads with the highest antioxidant potential. As for the antimicrobial activity, the results showed a selective effect of chemicals against Gram-positive and Gram-negative bacteria and Enterococcus faecalis and Staphylococcus aureus were the bacteria most affected by the phytochemicals. Based on the results achieved baby-leaf salads represent an important source of natural antioxidants and antimicrobial substances. Molecules 2013-04-19 18 4 Article 10.3390/molecules18044651 4651 4668 1420-3049 2013-04-19 doi: 10.3390/molecules18044651 Alfredo Aires Esperança Marques Rosa Carvalho Eduardo Rosa Maria Saavedra http://www.mdpi.com/1420-3049/18/4/4640 The aim of this research was to study the structural and textural characteristics of maize bran arabinoxylan (MBAX) microspheres. The laccase-induced cross-linking process was monitored by storage (G') and loss (G'') moduli changes in a 4% (w/v) MBAX solution. The G' and G'' values at the plateau region were 215 and 4 Pa, respectively. After gelation, the content of ferulic acid dimers decreased from 0.135 to 0.03 µg/mg MBAX, suggesting the formation of ferulated structures unreleased by mild alkaline hydrolysis. MBAX microspheres presented an average diameter of 531 µm and a swelling ratio value (q) of 18 g water/g MBAX. The structural parameters of MBAX microspheres were calculated from equilibrium swelling experiments, presenting an average mesh size of 52 nm. Microstructure and textural properties of dried MBAX microspheres were studied by scanning electron microscopy and nitrogen adsorption/desorption isotherms, respectively, showing a heterogeneous mesoporous and macroporous structure throughout the network. Molecules 2013-04-19 18 4 Communication 10.3390/molecules18044640 4640 4650 1420-3049 2013-04-19 doi: 10.3390/molecules18044640 Ana Martínez-López Elizabeth Carvajal-Millan Mario Miki-Yoshida Lorena Alvarez-Contreras Agustín Rascón-Chu Jaime Lizardi-Mendoza Yolanda López-Franco http://www.mdpi.com/1420-3049/18/4/4628 We report here the preparation of asymmetrical phthalocyanine dimers 1a–3a, which are endowed with novel charge transfer bands at 1,151–1,154 nm and strong NIR luminescences at 840–860 nm and 1,600–1,650 nm. Through H-bonding interaction, 1a–3a are inclined to self-assemble into hexrod nanotubes at the interface of CHCl3 and CH3OH. Our results provide further insights into the interaction in molecular dimers, and suggest that 1a–3a have potential application in magnets and supramolecular architectures. Molecules 2013-04-19 18 4 Communication 10.3390/molecules18044628 4628 4639 1420-3049 2013-04-19 doi: 10.3390/molecules18044628 Guoqing Huang Jianxi Li Fangdi Cong Chao Li Xixi Chu Yanyan Meng Guotong Du Xiguang Du http://www.mdpi.com/1420-3049/18/4/4613 Ten 1,4-disubstituted 1,2,3-triazoles were synthesized from one of 1-(azido-methyl)benzene, 1-(azidomethyl)-4-fluorobenzene, 1-(azidomethyl)-4-chlorobenzene, 1-(azidomethyl)-4-bromobenzene or 1-(azidomethyl)-4-iodobenzene, generated in situ from sodium azide and the corresponding benzyl halide, and dipropargyl uracil or dipropargyl thymine. Optimal experimental conditions were established for the conventional click chemistry. The corrosion inhibiting properties of some of these compounds, which were determined by means of an electrochemical technique, are also presented. Molecules 2013-04-18 18 4 Article 10.3390/molecules18044613 4613 4627 1420-3049 2013-04-18 doi: 10.3390/molecules18044613 Guillermo Negrón-Silva Rodrigo González-Olvera Deyanira Angeles-Beltrán Nidia Maldonado-Carmona Araceli Espinoza-Vázquez Manuel Palomar-Pardavé Mario Romero-Romo Rosa Santillan http://www.mdpi.com/1420-3049/18/4/4599 Covalently functionalized multi-walled carbon nanotubes (MWNTs) were prepared by grafting well-defined thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) via click reactions. First, azide-terminated poly(N-isopropylacrylamide) (N3-PNIPAM) was synthesized by reversible addition fragmentation chain-transfer (RAFT) polymerization, and then the N3-PNIPAM moiety was connected onto MWNTs by click chemistry. The products were characterized by means of FT-IR, TGA and TEM. The results show that the modification of MWNTs is very successful and MWNTs functionalized by N3-PNIPAM (MWNTs-PNIPAM) have good solubility and stability in water. TEM images show the functionalized MWNTs are dispersed individually, indicating that the bundles of original MWNTs are separated into individual tubes by surface modification with polymer chains. These MWNTs modified with PNIPAM represent a potential nano-material for preparation of hydrophilic composite materials. Molecules 2013-04-18 18 4 Article 10.3390/molecules18044599 4599 4612 1420-3049 2013-04-18 doi: 10.3390/molecules18044599 Xin Su Ya Shuai Zanru Guo Yujun Feng http://www.mdpi.com/1420-3049/18/4/4588 The chemical composition of the essential oils from leaves, bark and wood of Cassia bakeriana Craib. was determined by gas chromatography (GC) and gas chromatography–mass spectrometry (GC-MS). Alcohols, aldehydes and fatty acids were the major components in leaf and bark oil, while wood essential oil was rich in fatty acids. Terpenes such as linalool, (E)-nerolidol and phytol were present in low concentrations. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated using the microdilution method, as was the cell viability test carried out with Vero cells. The oils from leaves and bark showed high antimicrobial activity, with minimum inhibitory concentrations between 62.5 and 125 µg·mL−1 for most of the tested bacteria, including Streptococcus mutans, the main etiological agent of dental caries. Leaves oil displayed the lowest cytotoxic effect (EC50 of 153 µg·mL−1), while wood oil exhibited the highest toxicity to Vero cells. C. bakeriana oils are thus a source of biologically active compounds against aerobic and anaerobic oral microorganisms. This study is the first report on the chemical composition, antimicrobial activity and cytotoxicity of C. bakeriana. Molecules 2013-04-18 18 4 Article 10.3390/molecules18044588 4588 4598 1420-3049 2013-04-18 doi: 10.3390/molecules18044588 Luís Cunha Sérgio de Morais Carlos Martins Mário Martins Roberto Chang Francisco de Aquino Alberto de Oliveira Thaís Moraes Fabrício Machado Cláudio da Silva Evandro do Nascimento http://www.mdpi.com/1420-3049/18/4/4573 Virgin oils obtained from seeds of Camellia oleifera (CO), Camellia reticulata (CR) and Camellia sasanqua (CS) were studied for their triacylglyceride composition, antioxidant and antimicrobial activities. Levels of fatty acids determined by 1H-nuclear magnetic resonance analysis were similar to those reported for olive oils (82.30%–84.47%; 5.69%–7.78%; 0.26%–0.41% and 8.04%–11.2%, for oleic, linoleic, linolenic and saturated acids, respectively). The CR oil showed the best antioxidant potential in the three in vitro models tested. With regard to EC50 values (µg/mL), the order in DPPH radical-scavenging was CR (33.48) < CO (35.20) < CS (54.87). Effectiveness in reducing power was CR (2.81) < CO (3.09) < CS (5.32). IC50 for LPO inhibition were 0.37, 0.52 and 0.75 µg/mL for CR, CO and CS, respectively. All the oils showed antimicrobial activity, and exhibited different selectivity and MICs for each microorganism tested (E. coli, B. cereus and C. albicans). B. cereus was the less sensitive species (MIC: 52.083 ± 18.042 for CO; 41.667 ± 18.042 for CR; 104.167 ± 36.084 for CS mg/mL) and the E. coli was the most sensitive to camellia oil’s effect. The standard gentamicin presented higher MIC for E. coli (4.2) than the CR (MIC= 2.6) and CO (MIC = 3.9) oils. Molecules 2013-04-18 18 4 Article 10.3390/molecules18044573 4573 4587 1420-3049 2013-04-18 doi: 10.3390/molecules18044573 Xesús Feás Leticia Estevinho Carmen Salinero Pilar Vela María Sainz María Vázquez-Tato Julio Seijas