Molecules

10 pages, 1251 KiB

Open AccessArticle

The Role of Concentration and Solvent Character in the Molecular Organization of Humic Acids

by Martina Klučáková^* and Kateřina Věžníková

Materials Research Centre, Faculty of Chemistry, Brno University of Technology, Purkyňova 118/464, Brno 612 00, Czech Republic

Molecules 2016, 21(11), 1410; https://doi.org/10.3390/molecules21111410 - 27 Oct 2016

Cited by 15 | Viewed by 5363

Abstract

The molecular organization of humic acids in different aqueous solutions was studied over a wide concentration range (0.01–10 g·dm⁻³). Solutions of humic acids were prepared in three different media: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic [...] Read more.

The molecular organization of humic acids in different aqueous solutions was studied over a wide concentration range (0.01–10 g·dm⁻³). Solutions of humic acids were prepared in three different media: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic sample. Potentiometry, conductometry, densitometry, and high resolution ultrasound spectrometry were used in order to investigate conformational changes in the humic systems. The molecular organization of humic acids in the studied systems could be divided into three concentration ranges. The rearrangements were observed at concentrations of ~0.02 g·dm⁻³ and ~1 g·dm⁻³. The first “switch-over point” was connected with changes in the hydration shells of humic particles resulting in changes in their elasticity. The compressibility of water in the hydration shells is less than the compressibility of bulk water. The transfer of hydration water into bulk water increased the total compressibility of the solution, reducing the ultrasonic velocity. The aggregation of humic particles and the formation of rigid structures in systems with concentrations higher than 1 g·dm⁻³ was detected. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 389 KiB

Open AccessArticle

Antimalarial Activity of the Chemical Constituents of the Leaf Latex of Aloe pulcherrima Gilbert and Sebsebe

by Tekleab Teka¹, Daniel Bisrat², Mariamawit Yonathan Yeshak² and Kaleab Asres^2,*

¹ Department of Pharmacy, College of Health Sciences, Wollo University, P.O. Box 1145, Dessie, Ethiopia

² Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia

Molecules 2016, 21(11), 1415; https://doi.org/10.3390/molecules21111415 - 28 Oct 2016

Cited by 24 | Viewed by 5228

Abstract

Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has [...] Read more.

Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has proven to be more effective and inexpensive. The leaves of Aloe pulcherrima Gilbert and Sebsebe, an endemic Ethiopian plant, are locally used for the treatment of malaria and other infectious diseases. Application of the leaf latex of A. pulcherrima on preparative silica gel TLC led to the isolation of two C-glycosylated anthrones, identified as nataloin (1) and 7-hydroxyaloin (2) by spectroscopic techniques (UV, IR, ¹H- and ¹³C-NMR, HR-ESIMS). Both the latex and isolated compounds displayed antimalarial activity in a dose-independent manner using a four-day suppressive test, with the highest percent suppression of 56.2% achieved at 200 mg/kg/day for 2. The results indicate that both the leaf latex of A. pulcherrima and its two major constituents are endowed with antiplasmodial activities, which support the traditional use of the leaves of the plant for the treatment of malaria. Full article

(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)

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15 pages, 4020 KiB

Open AccessArticle

Piceatannol Exerts Anti-Obesity Effects in C57BL/6 Mice through Modulating Adipogenic Proteins and Gut Microbiota

by Yen-Chen Tung¹, Yu-Hsuan Lin¹, Hong-Jhang Chen¹, Shen-Chieh Chou², An-Chin Cheng³, Nagabhushanam Kalyanam⁴

, Chi-Tang Ho⁵ and Min-Hsiung Pan^1,6,7,*

¹ Institute of Food Sciences and Technology, National Taiwan University, Taipei 10617, Taiwan

² Department of Biological Science & Technology, China Medical University, Taichung 40402, Taiwan

³ Department of Tourism, Food and Beverage Management, Chang Jung Christian University, Tainan 71101, Taiwan

⁴ Sabinsa Corporation, East Windsor, NJ 08520, USA

⁵ Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA

⁶ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan

⁷ Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan

Molecules 2016, 21(11), 1419; https://doi.org/10.3390/molecules21111419 - 25 Oct 2016

Cited by 78 | Viewed by 10299

Abstract

Obesity is a global health concern. Piceatannol (Pic), an analog of resveratrol (Res), has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD)-induced obese animal model. The results showed that Pic significantly reduced [...] Read more.

Obesity is a global health concern. Piceatannol (Pic), an analog of resveratrol (Res), has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD)-induced obese animal model. The results showed that Pic significantly reduced mouse body weight in a dose-dependent manner without affecting food intake. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) levels, and blood glucose (GLU) were significantly lowered in Pic-treated groups. Pic significantly decreased the weight of liver, spleen, perigonadal and retroperitoneal fat compared with the HFD group. Pic significantly reduced the adipocyte cell size of perigonadal fat and decreased the weight of liver. Pic-treated mice showed higher phosphorylated adenosine 5′-monophosphate-activated protein kinase (pAMPK) and phosphorylated acetyl-CoA carboxylase (pACC) protein levels and decreased protein levels of CCAAT/enhancer-binding protein C/EBPα, peroxisome proliferator-activated receptor PPARγ and fatty acid synthase (FAS), resulting in decreased lipid accumulation in adipocytes and the liver. Pic altered the composition of the gut microbiota by increasing Firmicutes and Lactobacillus and decreasing Bacteroidetes compared with the HFD group. Collectively, these results suggest that Pic may be a candidate for obesity treatment. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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20 pages, 803 KiB

Open AccessArticle

Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates

by Iwona E. Głowacka^1,*, Rafał Gulej¹, Piotr Grzonkowski¹, Graciela Andrei², Dominique Schols², Robert Snoeck² and Dorota G. Piotrowska¹

¹ Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland

² Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

Molecules 2016, 21(11), 1420; https://doi.org/10.3390/molecules21111420 - 26 Oct 2016

Cited by 11 | Viewed by 5854

Abstract

A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency [...] Read more.

A novel series of diethyl {4-[(5-substituted-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates designed as analogues of amonafide was synthesized. All phosphonates were assessed for antiviral activity against a broad range of DNA and RNA viruses and several of them showed potency against varicella-zoster virus (VZV) [EC₅₀ (50% effective concentration) = 27.6–91.5 μM]. Compound 16b exhibited the highest activity against a thymidine kinase-deficient (TK⁻) VZV strain (EC₅₀ = 27.59 μM), while 16d was the most potent towards TK⁺ VZV (EC₅₀ = 29.91 μM). Cytostatic properties of the compounds 14a–i–17a–i were studied on L1210, CEM, HeLa and HMEC-1 cell lines and most of them were slightly cytostatic for HeLa [IC₅₀ (50% inhibitory concentration) = 29–130 µM] and L1210 cells [IC₅₀ (50% inhibitory concentration) = 14–142 µM]. Full article

(This article belongs to the Section Bioorganic Chemistry)

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16 pages, 889 KiB

Open AccessArticle

Novel Halogenated Pyrazine-Based Chalcones as Potential Antimicrobial Drugs

by Marta Kucerova-Chlupacova^1,*

, Veronika Vyskovska-Tyllova¹, Lenka Richterova-Finkova¹, Jiri Kunes², Vladimir Buchta^3,4, Marcela Vejsova^3,4, Pavla Paterova^3,4, Lucia Semelkova¹, Ondrej Jandourek¹

and Veronika Opletalova¹

¹ Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

² Department of Inorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

³ Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

⁴ Department of Clinical Microbiology, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic

Molecules 2016, 21(11), 1421; https://doi.org/10.3390/molecules21111421 - 27 Oct 2016

Cited by 31 | Viewed by 8301

Abstract

Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal [...] Read more.

Chalcones, i.e., compounds with the chemical pattern of 1,3-diphenylprop-2-en-1-ones, exert a wide range of bio-activities, e.g., antioxidant, anti-inflammatory, anticancer, anti-infective etc. Our research group has been focused on pyrazine analogues of chalcones; several series have been synthesized and tested in vitro on antifungal and antimycobacterial activity. The highest potency was exhibited by derivatives with electron withdrawing groups (EWG) in positions 2 and 4 of the ring B. As halogens also have electron withdrawing properties, novel halogenated derivatives were prepared by Claisen-Schmidt condensation. All compounds were submitted for evaluation of their antifungal and antibacterial activity, including their antimycobacterial effect. In the antifungal assay against eight strains of selected fungi, growth inhibition of Candida glabrata and Trichophyton interdigitale (formerly T. mentagrophytes) was shown by non-alkylated derivatives with 2-bromo or 2-chloro substitution. In the panel of selected bacteria, 2-chloro derivatives showed the highest inhibitory effect on Staphylococcus sp. In addition, all products were also screened for their antimycobacterial activity against Mycobacterium tuberculosis H37RV My 331/88, M. kansasii My 235/80, M. avium 152/80 and M. smegmatis CCM 4622. Some of the examined compounds, inhibited growth of M. kansasii and M. smegmatis with minimum inhibitory concentrations (MICs) comparable with those of isoniazid. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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14 pages, 1620 KiB

Open AccessArticle

Substituent Inductive Effects on the Electrochemical Oxidation of Flavonoids Studied by Square Wave Voltammetry and Ab Initio Calculations

by Netzahualcóyotl Arroyo-Currás^1,†, Víctor M. Rosas-García²

and Marcelo Videa^1,3,*

¹ Departament of Chemistry, Tecnológico de Monterrey, Av. E. Garza Sada 2501 Sur, Monterrey 64849, N.L., Mexico

² Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Pedro de Alba S-N Cd. Universitaria, San Nicolás De Los Garza 66451, N.L., Mexico

³ School of Engineering and Science, Tecnológico de Monterrey, Av. E. Garza Sada 2501 Sur, Monterrey 64849, N.L., Mexico

^† Current address: Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA 93106, USA

Molecules 2016, 21(11), 1422; https://doi.org/10.3390/molecules21111422 - 27 Oct 2016

Cited by 22 | Viewed by 6705

Abstract

Flavonoids are natural products commonly found in the human diet that show antioxidant, anti-inflammatory and anti-hepatotoxic activities. These nutraceutical properties may relate to the electrochemical activity of flavonoids. To increase the understanding of structure–electrochemical activity relations and the inductive effects that OH substituents [...] Read more.

Flavonoids are natural products commonly found in the human diet that show antioxidant, anti-inflammatory and anti-hepatotoxic activities. These nutraceutical properties may relate to the electrochemical activity of flavonoids. To increase the understanding of structure–electrochemical activity relations and the inductive effects that OH substituents have on the redox potential of flavonoids, we carried out square-wave voltammetry experiments and ab initio calculations of eight flavonoids selected following a systematic variation in the number of hydroxyl substituents and their location on the flavan backbone: three flavonols, three anthocyanidins, one anthocyanin and the flavonoid backbone flavone. We compared the effect that the number of –OH groups in the ring B of flavan has on the oxidation potential of the flavonoids considered, finding linear correlations for both flavonols and anthocyanidins (

R^{2} = 0.98

). We analyzed the effects that position and number of –OH substituents have on electron density distributions via ab initio quantum chemical calculations. We present direct correlations between structural features and oxidation potentials that provide a deeper insight into the redox chemistry of these molecules. Full article

(This article belongs to the Special Issue Organic Electrochemistry)

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14 pages, 1861 KiB

Open AccessArticle

Discrimination and Nitric Oxide Inhibitory Activity Correlation of Ajwa Dates from Different Grades and Origin

by Nur Ashikin Abdul-Hamid¹, Ahmed Mediani², M. Maulidiani¹, Faridah Abas^1,2,*, Intan Safinar Ismail^1,3

, Khozirah Shaari^1,3 and Nordin H. Lajis^1,*

¹ Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Malaysia

² Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Malaysia

³ Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Malaysia

Molecules 2016, 21(11), 1423; https://doi.org/10.3390/molecules21111423 - 28 Oct 2016

Cited by 9 | Viewed by 5856

Abstract

This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO) inhibitory [...] Read more.

This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO) inhibitory activity. Identification of the metabolites was generated using ¹H-NMR spectroscopy metabolomics analyses utilizing multivariate methods. The NO inhibitory activity was determined using a Griess assay. Multivariate data analysis, for both supervised and unsupervised approaches, showed clusters among different grades of Ajwa dates obtained from different farms. The compounds that contribute towards the observed separation between Ajwa samples were suggested to be phenolic compounds, ascorbic acid and phenylalanine. Ajwa dates were shown to have different metabolite compositions and exhibited a wide range of NO inhibitory activity. It is also revealed that Ajwa Grade 1 from the al-Aliah farm exhibited more than 90% NO inhibitory activity compared to the other grades and origins. Phenolic compounds were among the compounds that played a role towards the greater capacity of NO inhibitory activity shown by Ajwa Grade 1 from the al-Aliah farm. Full article

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13 pages, 1703 KiB

Open AccessArticle

Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats

by Yoon Hee Lee¹, Bora Jin¹, Sung Hyun Lee¹, MiKyung Song¹, HyeonHui Bae¹, Byung Jae Min¹, Juyeon Park¹, Donghun Lee² and Hocheol Kim^2,*

¹ Korea Institute of Science and Technology for Eastern Medicine (KISTEM), NeuMed Inc., Seoul 130-701, Korea

² Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Korea

Molecules 2016, 21(11), 1424; https://doi.org/10.3390/molecules21111424 - 25 Oct 2016

Cited by 53 | Viewed by 7236

Abstract

It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. [...] Read more.

It is well established that obesity causes a variety of chronic diseases such as cardiovascular diseases and diabetes. Despite the diligent scientific efforts to find effective ways to lower the level of obesity, the size of obese population grows continuously around the world. Here we present the results that show feeding diet containing HT048, a mixture of the extracts of Crataegus pinnatifida leaves and Citrus unshiu peel, two of the well-known traditional herbal medicines in Eastern Asia, decreases obesity in rats. We fed rats with five different diets for 10 weeks: chow diet (STD), high-fat diet (HFD), high-fat diet with 0.04% orlistat, a drug to treat obesity (HFD + Orlistat), high-fat diet with 0.2% HT048 (w/w; HFD + 0.2% HT048), and high-fat diet with 0.6% HT048 (w/w; HFD + 0.6% HT048). It was found that both body and total white adipose tissue weight of HT048 groups significantly decreased compared to those of the HFD group. Moreover, HT048 decreased serum insulin levels in HFD-fed obese rats. At the molecular level, HT048 supplementation downregulated genes involved in lipogenesis, gluconeogenesis, and adipogenesis, while the expression level of β-oxidation genes was increased. Supplementation-drug interactions are not likely as HFD and HT048-containing diet did not significantly induce genes encoding CYPs. Collectively, this study suggests that HT048 taken as dietary supplement helps to decrease obesity and insulin resistance in HFD-fed obese rats. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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15 pages, 885 KiB

Open AccessArticle

Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats

by Israel Pérez-Torres^1,†

, Juan Carlos Torres-Narváez^2,†, José Pedraza-Chaverri³

, María Esther Rubio-Ruiz⁴

, Eulises Díaz-Díaz⁵, Leonardo Del Valle-Mondragón², Raúl Martínez-Memije⁶, Elvira Varela López⁴ and Verónica Guarner-Lans^4,*

¹ Department of Pathology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico

² Department of Pharmacology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico

³ Facultad de Química, Department of Biology, Edificio B, Segundo Piso, Laboratorio 209, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Mexico City 04510, Mexico

⁴ Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico

⁵ Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Vasco de Quiroga 15, Sección XVI, Tlalpan, Mexico City 14000, Mexico

⁶ Electromechanical Instrumentation, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico

^† Israel Pérez-Torres and Juan Carlos Torres-Narváez, share the first authorship of this paper.

Molecules 2016, 21(11), 1425; https://doi.org/10.3390/molecules21111425 - 26 Oct 2016

Cited by 35 | Viewed by 9272

Abstract

The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats [...] Read more.

The antioxidant properties of aged garlic extract (AGE) on cardiovascular functioning (CF) in metabolic syndrome (MS) remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS), MS rats (30% sucrose in drinking water from weaning) plus saline solution (MS + SS), control rats receiving AGE (C + AGE 125 mg/Kg/12 h) and MS rats with AGE (MS + AGE) were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01). Cholesterol was decreased by AGE (p = 0.05). Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05). Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001). Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation) and AGE improved it (p = 0.001). Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001). Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01). In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties. Full article

(This article belongs to the Special Issue The Chemistry of Alliums)

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17 pages, 1605 KiB

Open AccessArticle

Assessment of the Presence and Strength of H-Bonds by Means of Corrected NMR

by Steve Scheiner

Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA

Molecules 2016, 21(11), 1426; https://doi.org/10.3390/molecules21111426 - 27 Oct 2016

Cited by 32 | Viewed by 9211

Abstract

The downfield shift of the NMR signal of the bridging proton in a H-bond (HB) is composed of two elements. The formation of the HB causes charge transfer and polarization that lead to a deshielding. A second factor is the mere presence of [...] Read more.

The downfield shift of the NMR signal of the bridging proton in a H-bond (HB) is composed of two elements. The formation of the HB causes charge transfer and polarization that lead to a deshielding. A second factor is the mere presence of the proton-accepting group, whose electron density and response to an external magnetic field induce effects at the position of the bridging proton, exclusive of any H-bonding phenomenon. This second positional shielding must be subtracted from the full observed shift in order to assess the deshielding of the proton caused purely by HB formation. This concept is applied to a number of H-bonded systems, both intramolecular and intermolecular. When the positional shielding is removed, the remaining chemical shift is in much better coincidence with other measures of HB strength. Full article

(This article belongs to the Special Issue Intramolecular Hydrogen Bonding 2017)

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15 pages, 2540 KiB

Open AccessArticle

Properties of Manganese(III) Ferrocenyl-β-Diketonato Complexes Revealed by Charge Transfer and Multiplet Splitting in the Mn 2p and Fe 2p X-Ray Photoelectron Envelopes

by Blenerhassitt E. Buitendach¹, Elizabeth Erasmus¹, J. W. (Hans) Niemantsverdriet² and Jannie C. Swarts^1,*

¹ Department of Chemistry, University of the Free State, Bloemfontein 9300, South Africa

² SynCat@DIFFER, Syngaschem BV, De Zaale 20, Eindhoven 5612 AJ, The Netherlands

Molecules 2016, 21(11), 1427; https://doi.org/10.3390/molecules21111427 - 26 Oct 2016

Cited by 29 | Viewed by 9301

Abstract

A series of ferrocenyl-functionalized β-diketonato manganese(III) complexes, [Mn(FcCOCHCOR)₃] with R = CF₃, CH₃, Ph (phenyl) and Fc (ferrocenyl) was subjected to a systematic XPS study of the Mn 2p_3/2 and Fe 2p_3/2 core-level photoelectron lines [...] Read more.

A series of ferrocenyl-functionalized β-diketonato manganese(III) complexes, [Mn(FcCOCHCOR)₃] with R = CF₃, CH₃, Ph (phenyl) and Fc (ferrocenyl) was subjected to a systematic XPS study of the Mn 2p_3/2 and Fe 2p_3/2 core-level photoelectron lines and their satellite structures. A charge-transfer process from the β-diketonato ligand to the Mn(III) metal center is responsible for the prominent shake-up satellite peaks of the Mn 2p photoelectron lines and the shake-down satellite peaks of the Fe 2p photoelectron lines. Multiplet splitting simulations of the photoelectron lines of the Mn(III) center of [Mn(FcCOCHCOR)₃] resemble the calculated Mn 2p_3/2 envelope of Mn³⁺ ions well, indicating the Mn(III) centers are in the high spin state. XPS spectra of complexes with unsymmetrical β-diketonato ligands (i.e., R not Fc) were described with two sets of multiplet splitting peaks representing fac and the more stable mer isomers respectively. Stronger electron-donating ligands stabilize fac more than mer isomers. The sum of group electronegativities, Σχ_R, of the β-diketonato pendant side groups influences the binding energies of the multiplet splitting and charge transfer peaks in both Mn and Fe 2p_3/2 photoelectron lines, the ratio of satellite to main peak intensities, and the degree of covalence of the Mn–O bond. Full article

(This article belongs to the Section Organometallic Chemistry)

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8 pages, 2534 KiB

Open AccessArticle

Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A

by Bing Zhang^1,2,†

, Xiyan Wang^2,†, Lin Wang², Shuiye Chen², Dongxue Shi² and Hongsu Wang^1,2,*

¹ College of Food Science and Engineering, Jilin University, Changchun 130062, China

² College of Veterinary Medicine, Jilin University, Changchun 130062, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1428; https://doi.org/10.3390/molecules21111428 - 26 Oct 2016

Cited by 19 | Viewed by 5649

Abstract

The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded [...] Read more.

The intractability of bacterial resistance presents a dilemma for therapies against Staphylococcus aureus (S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacterial infections. In the present study, the inhibitory effect of dryocrassin ABBA (ABBA) against SrtA and its molecular basis has been examined. Fluorescence resonance energy transfer (FRET) assays were used to determine the inhibitory activity of ABBA against SrtA. To identify the mechanism underlying this activity, molecular dynamics simulations and mutagenesis assays were applied, and the results revealed that the direct engagement of SrtA via ABBA through binding to V166 and V168 significantly attenuated the catalytic activity of SrtA. Taken together, these findings indicated that ABBA is a potential novel antimicrobial agent for S. aureus infection via targeting SrtA. Full article

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12 pages, 3320 KiB

Open AccessArticle

A Combined Molecular Cloning and Mass Spectrometric Method to Identify, Characterize, and Design Frenatin Peptides from the Skin Secretion of Litoria infrafrenata

by Di Wu^1,†

, Yitian Gao^1,†, Lei Wang¹, Xinping Xi¹, Yue Wu¹, Mei Zhou¹

, Yingqi Zhang^2,*, Chengbang Ma^1,*, Tianbao Chen¹

and Chris Shaw¹

¹ Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK

² Department of Emergency Medicine, The First Hospital of Hebei Medical University, Shijiazhuang 050031, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1429; https://doi.org/10.3390/molecules21111429 - 26 Oct 2016

Cited by 14 | Viewed by 5361

Abstract

Amphibian skin secretions are unique sources of bioactive molecules, particularly bioactive peptides. In this study, the skin secretion of the white-lipped tree frog (Litoria infrafrenata) was obtained to identify peptides with putative therapeutic potential. By utilizing skin secretion-derived mRNA, a cDNA [...] Read more.

Amphibian skin secretions are unique sources of bioactive molecules, particularly bioactive peptides. In this study, the skin secretion of the white-lipped tree frog (Litoria infrafrenata) was obtained to identify peptides with putative therapeutic potential. By utilizing skin secretion-derived mRNA, a cDNA library was constructed, a frenatin gene was cloned and its encoded peptides were deduced and confirmed using RP-HPLC, MALDI-TOF and MS/MS. The deduced peptides were identified as frenatin 4.1 (GFLEKLKTGAKDFASAFVNSIKGT) and a post-translationally modified peptide, frenatin 4.2 (GFLEKLKTGAKDFASAFVNSIK.NH₂). Antimicrobial activity of the peptides was assessed by determining their minimal inhibitory concentrations (MICs) using standard model microorganisms. Through studying structure–activity relationships, analogues of the two peptides were designed, resulting in synthesis of frenatin 4.1a (GFLEKLKKGAKDFASALVNSIKGT) and frenatin 4.2a (GFLLKLKLGAKLFASAFVNSIK.NH₂). Both analogues exhibited improved antimicrobial activities, especially frenatin 4.2a, which displayed significant enhancement of broad spectrum antimicrobial efficiency. The peptide modifications applied in this study, may provide new ideas for the generation of leads for the design of antimicrobial peptides with therapeutic applications. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 862 KiB

Open AccessArticle

Two New Stilbenoids from the Aerial Parts of Arundina graminifolia (Orchidaceae)

by Florence Auberon^1,*

, Opeyemi Joshua Olatunji¹

, Stéphanie Krisa², Cyril Antheaume³, Gaëtan Herbette⁴

, Frédéric Bonté⁵, Jean-Michel Mérillon² and Annelise Lobstein¹

¹ Laboratory of Pharmacognosy and Bioactive Natural Products, Faculty of Pharmacy, Strasbourg University, Illkirch-Graffenstaden 67400, France

² GESVAB Group, Oenology Research Unit, EA 4577, USC 1366 INRA, ISVV, Faculty of Pharmacy, Bordeaux University, Villenave d’Ornon 33140, France

³ Laboratoire Insulaire du Vivant et de l’Environnement, EA 4243, New-Caledonia University, BP R4, Noumea CEDEX 98851, New Caledonia

⁴ Spectropôle, FR1739, Aix-Marseille University, Campus de St Jerome-Service 511, Marseille 13397, France

⁵ Louis Vuitton Moët et Hennessy Recherche, 185 avenue de Verdun, St Jean de Braye 45800, France

Molecules 2016, 21(11), 1430; https://doi.org/10.3390/molecules21111430 - 27 Oct 2016

Cited by 29 | Viewed by 4931

Abstract

Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (4–10) were isolated from the aerial parts [...] Read more.

Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (4–10) were isolated from the aerial parts of the Asian orchid Arundina graminifolia. The structures of the isolated compounds were elucidated by spectroscopic methods, including extensive 1D, 2D NMR (heteronuclear single quantum coherence (HSQC), heteronuclear multiple-bond correlation spectroscopy (HMBC), and HR-ESI-MS techniques, as well as comparison with respective literature reports. The cytoprotective activity of the isolated compounds were evaluated for their ability to reduce beta amyloid induced toxicity on undifferentiated PC12 cells. Compound 8 showed moderate cytoprotective activity at 0.5 µmol/L (71% of cell viability) while the other compounds showed no significant activity at the highest concentration tested. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1819 KiB

Open AccessArticle

Comparative Transcriptomic Analysis of Grape Berry in Response to Root Restriction during Developmental Stages

by Feng Leng¹, Qiong Lin^1,2, Di Wu¹, Shiping Wang³, Dengliang Wang⁴ and Chongde Sun^1,*

¹ Laboratory of Fruit Quality Biology, The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Zijingang Campus, Hangzhou 310058, China

² Institute of Agro-Food Science and Technology, Chinese Academy of Agricultural Sciences/Key Opening Laboratory of Agricultural Products Processing and Quality Control, Ministry of Agriculture, Beijing 100193, China

³ School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China

⁴ Quzhou Academy of Agricultural Science, Quzhou 324000, China

Molecules 2016, 21(11), 1431; https://doi.org/10.3390/molecules21111431 - 28 Oct 2016

Cited by 24 | Viewed by 5992

Abstract

Root restriction improved berry quality by being involved in diverse aspects of grapevine life. However, the molecular mechanism driving this process is not understood very well. In this study, the ‘Summer Black’ grape berry (Vitis vinifera × V. labrusca) under root [...] Read more.

Root restriction improved berry quality by being involved in diverse aspects of grapevine life. However, the molecular mechanism driving this process is not understood very well. In this study, the ‘Summer Black’ grape berry (Vitis vinifera × V. labrusca) under root restriction was investigated, which showed an increase of total soluble solids (TSS), color index of red grapes (CIRG) value, anthocyanins accumulation, total phenolics and total procyanidins contents during berry development compared with those in control berries. The transcriptomic changes induced by root restriction in ‘Summer Black’ grape over the course of berry development were analyzed by RNA-Seq method. A total of 29,971 genes were generated in ‘Summer Black’ grape berry during development, among which, 1606 genes were significantly responded to root restriction. Furthermore, 1264, 313, 141, 246 and 19 sequences were significantly changed at S1, S2, S3, S4 and S5 sample points, respectively. The gene (VIT_04s0023g02290) predicted as a salicylate O-methyltransferase was differentially expressed in all developmental stages. Gene Ontology (GO) enrichment showed that response to organic nitrogen, response to endogenous stimulus, flavonoid metabolic process, phenylpropanoid biosynthetic process and cell wall macromolecule metabolic process were the main significant differential categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed plant–pathogen interaction, plant hormone signal transduction, flavone and flavonol biosynthesis, flavonoid biosynthesis and glucosinolate biosynthesis were the main significant differential pathways. The results of the present study provided a genetic base for the understanding of grape berry fruit quality improvement under root restriction. Full article

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11 pages, 798 KiB

Open AccessArticle

Alkaloids with Activity against the Zika Virus Vector Aedes aegypti (L.)—Crinsarnine and Sarniensinol, Two New Crinine and Mesembrine Type Alkaloids Isolated from the South African Plant Nerine sarniensis

by Marco Masi¹

, Antonio Cala^1,2

, Nurhayat Tabanca^3,4

, Alessio Cimmino¹

, Ivan R. Green⁵, Jeffrey R. Bloomquist³

, Willem A. L. Van Otterlo⁴, Francisco A. Macias² and Antonio Evidente^1,*

¹ Department of Chemical Sciences, University of Naples “Federico II”, Complesso Universitario Monte S. Angelo, Via Cintia 4, 80126 Napoli, Italy

² Allelopathy Group, Department of Organic Chemistry, School of Science, Institute of Biomolecules (INBIO), University of Cádiz, C/República Saharaui 7, 11510 Puerto Real, Cádiz, Spain

³ Department of Entomology and Nematology, Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA

⁴ U.S. Department of Agriculture-Agricultural Research Service, Subtropical Horticulture Research Station, 13601 Old Cutler Rd., Miami, FL 33158, USA

⁵ Department of Chemistry and Polymer Science, University of Stellenbosch, Private Bag X1, Matieland, 7602 Stellenbosch, South Africa

Molecules 2016, 21(11), 1432; https://doi.org/10.3390/molecules21111432 - 27 Oct 2016

Cited by 37 | Viewed by 7569

Abstract

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) [...] Read more.

Two new Amaryllidaceae alkaloids, belonging to the mesembrine- and crinine-types, named crinsarnine (1) and sarniensinol (2), were isolated from the dried bulbs of Nerine sarniensis together with bowdensine (3), sarniensine (4), hippadine (5) and 1-O-acetyl-lycorine (6). Crinsarnine (1) and sarniensinol (2) were characterized using spectroscopic and chiroptical methods as (1S,2S,4aR,10bS)-2,7-dimethoxy-1,2,3,4,4a,6-hexahydro-5,11b-ethano[1,3]dioxolo-[4,5-j]phenanthridin-1-yl acetate and (6-(3aR,4Z,6S,7aS)-6-methoxy-1-methyl-2,3,3a,6,7,7a-hexa-hydro-1H-indol-3a-yl)benzo[d][1,3]dioxol-5-yl)methanol, respectively. Furthermore, the complete spectroscopic characterization of bowdensine (3) is reported for the first time. Compounds 1–6 were evaluated against the Orlando reference strain of Aedes aegypti. None of compounds showed mortality against 1st instar Ae. aegypti larvae at the concentrations tested. In adult topical bioassays, only 1 displayed adulticidal activity with an LD₅₀ = 2.29 ± 0.049 μg/mosquito. As regards the structure-activity relationship, the pretazettine and crinine scaffold in 2 and 4 and in 1 and 3 respectively, proved to be important for their activity, while the pyrrole[de]phenanthridine scaffold present in 5 and 6 was important for their reactivity. Among the pretazettine group compounds, opening of the B ring or the presence of a B ring lactone as well as the trans-stereochemistry of the A/B ring junction, appears to be important for activity, while in crinine-type alkaloids, the substituent at C-2 seems to play a role in their activity. Full article

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

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8 pages, 565 KiB

Open AccessArticle

Four New 2-(2-Phenylethyl)chromone Derivatives from Chinese Agarwood Produced via the Whole-Tree Agarwood-Inducing Technique

by Yang-Yang Liu^1,2, De-Li Chen²

, Jian-He Wei^1,2,*, Jian Feng², Zheng Zhang^1,2, Yun Yang^1,2 and Wei Zheng²

¹ Institute of Medicinal Plant Development (National Engineering Laboratory for Breeding of Endangered Medicinal Materials), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

² Hainan Branch of Institute of Medicinal Plant Development, Chinese Academy of Medicinal Sciences & Peking Union Medical College (Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine), Haikou 570311, China

Molecules 2016, 21(11), 1433; https://doi.org/10.3390/molecules21111433 - 27 Oct 2016

Cited by 24 | Viewed by 5265

Abstract

Four new 2-(2-phenylethyl)chromone derivatives (1–4) were isolated from the EtOH extract of Chinese agarwood produced via the whole-tree agarwood-inducing technique, coming from Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae). Their structures were elucidated by extensive spectroscopic methods, such as UV, IR, [...] Read more.

Four new 2-(2-phenylethyl)chromone derivatives (1–4) were isolated from the EtOH extract of Chinese agarwood produced via the whole-tree agarwood-inducing technique, coming from Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae). Their structures were elucidated by extensive spectroscopic methods, such as UV, IR, MS, 1D as well as 2D NMR. All of the isolates were then assessed for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7. Compound 1 exhibited significant inhibitory activity with an IC₅₀ value of 4.6 μM. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1257 KiB

Open AccessArticle

A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σ_p in [3+2] Cycloaddition Reactions of Aryl Azide/Alkyne Derivatives

by Hicham Ben El Ayouchia¹

, Hafid Anane¹

, Moulay Lahcen El Idrissi Moubtassim¹, Luis R. Domingo²

, Miguel Julve³

and Salah-Eddine Stiriba^1,3,*

¹ Laboratoire de Chimie Analytique et Moléculaire, Faculté Polydisciplinaire de Safi, Université Cadi Ayyad, Safi 46010, Morocco

² Departamento de Química Orgánica, Universidad de Valencia, Avda. Dr. Moliner 50, Burjassot 46100, Valencia, Spain

³ Instituto de Ciencia Molecular/ICMol, Universidad de Valencia, C/Catedrático José Beltrán No. 2, Paterna 46980, Valencia, Spain

Molecules 2016, 21(11), 1434; https://doi.org/10.3390/molecules21111434 - 27 Oct 2016

Cited by 9 | Viewed by 6699

Abstract

The relationship between the electrophilicity ω index and the Hammett constant σ_p has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT) [...] Read more.

The relationship between the electrophilicity ω index and the Hammett constant σ_p has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT) descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σ_p. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components. Full article

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

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11 pages, 1230 KiB

Open AccessArticle

Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

by Xiaolin Zhang^1,*

, Anmin Jiang², Hao Yu¹, Youyi Xiong¹, Guoliang Zhou¹, Meisong Qin¹, Jinfeng Dou¹ and Jianfei Wang^1,3,*

¹ The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China

² The School of Life Science, University of Science and Technology of China, Hefei 230032, China

³ The Ministry of Agriculture Key Laboratory of Microbial Organic Fertilizer, Bengbu 233030, China

Molecules 2016, 21(11), 1435; https://doi.org/10.3390/molecules21111435 - 28 Oct 2016

Cited by 26 | Viewed by 5788

Abstract

Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention [...] Read more.

Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations. Full article

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9 pages, 1061 KiB

Open AccessArticle

Penicitroamide, an Antimicrobial Metabolite with High Carbonylization from the Endophytic Fungus Penicillium sp. (NO. 24)

by Zi-Wei Feng¹, Meng-Meng Lv¹, Xue-Shuang Li¹, Liang Zhang¹, Cheng-Xiong Liu¹, Zhi-Yong Guo^1,*, Zhang-Shuang Deng^1,*, Kun Zou¹ and Peter Proksch²

¹ Hubei Key Laboratory of Natural Product Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China

² Institut für Pharmazeutische Biologie und Biotechnologie, Heirich-Heine University Dusseldorf, Universitätsstr. 1, Gebäude 26.23, Dusseldorf 40225, Germany

Molecules 2016, 21(11), 1438; https://doi.org/10.3390/molecules21111438 - 28 Oct 2016

Cited by 10 | Viewed by 5034

Abstract

Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves [...] Read more.

Penicitroamide (1), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves of Tapiscia sinensis Oliv. The structure of penicitroamide (1) features a bicyclo[3.2.1]octane core unit with a high degree of carbonylization (four carbonyl groups and one enol group). The chemical structure of penicitroamide (1) was elucidated by analysis of 1D-, 2D-NMR and MS data. In bioassays, penicitroamide (1) displayed antibacterial potency against two plant pathogens, Erwinia carotovora subsp. Carotovora (Jones) Bersey, et al. and Sclerotium rolfsii Sacc. with MIC₅₀ at 45 and 50 μg/mL. Compound 1 also showed 60% lethality against brine shrimp at 10 μg/mL. Penicitroamide (1) exhibited no significant activity against A549, Caski, HepG2 and MCF-7 cells with IC₅₀ > 50 μg/mL. Finally, the possible biosynthetic pathway of penicitroamide (1) was discussed. Full article

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

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13 pages, 3404 KiB

Open AccessArticle

Antioxidant Enzyme Activities and Lipid Oxidation in Rape (Brassica campestris L.) Bee Pollen Added to Salami during Processing

by Yawei Zhang^1,2, Fengtian Yang¹, Muneer Ahmed Jamali¹ and Zengqi Peng^1,*

¹ College of Food Science and Technology, National Center of Meat Quality and Safety Control, Nanjing Agricultural University, Nanjing 210095, China

² Synergetic Innovation Center of Food Safety and Nutrition, Nanjing 210095, China

Molecules 2016, 21(11), 1439; https://doi.org/10.3390/molecules21111439 - 28 Oct 2016

Cited by 28 | Viewed by 5869

Abstract

The present research investigated the antioxidant effect of rape (Brassica campestris L.) bee pollen (RBP) on salami during processing. Eight flavonoids in RBP ethanol extract were quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, and quercetin, rutin, and kaempferol were the major [...] Read more.

The present research investigated the antioxidant effect of rape (Brassica campestris L.) bee pollen (RBP) on salami during processing. Eight flavonoids in RBP ethanol extract were quantified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis, and quercetin, rutin, and kaempferol were the major bioactive compounds. The RBP ethanol extract exhibited higher total antioxidant capacity than 6-hydroxy-2,5,7,8-tertramethylchromancarboxylic acid (trolox) at the same concentration. The salami with 0.05% RBP extract had higher catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities than that of the control throughout the processing time (p < 0.05). Significant decreases in peroxide value (POV) and thiobarbituric acid-reactive substances (TBARS) were obtained in the final salami product with 0.05% RBP ethanol extract or 1% RBP (p < 0.05). These results suggested that RBP could improve oxidative stability and had a good potential as a natural antioxidant for retarding lipid oxidation. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 2530 KiB

Open AccessArticle

Screening Auxin Response, In Vitro Culture Aptitude and Susceptibility to Agrobacterium-Mediated Transformation of Italian Commercial Durum Wheat Varieties

by Wilma Sabetta^1,*

, Cristina Crosatti², Alexandra Soltész³

, Valentina Di Rienzo¹ and Cinzia Montemurro^1,4

¹ Sinagri S.r.l., Spin-off, University of Bari, Via Amendola 165/A, Bari 70126, Italy

² Council for Agricultural Research and Economics, Genomics Research Centre, Via S.Protaso 302, Fiorenzuola d’Arda (PC) 29017, Italy

³ Agricultural Institute, Centre for Agricultural Research, Hungarian Academy of Sciences, Brunszvik u. 2., Martonvásár H-2462, Hungary

⁴ Department of Soil, Plant and Food Sciences, University of Bari, Via Amendola 165/A, Bari 70126, Italy

Molecules 2016, 21(11), 1440; https://doi.org/10.3390/molecules21111440 - 28 Oct 2016

Cited by 2 | Viewed by 5143

Abstract

The development of a robust Agrobacterium-mediated transformation protocol for a recalcitrant species like durum wheat requires the identification and optimization of factors affecting T-DNA delivery and plant regeneration. The purpose of this research was to compare the behavior of diverse durum wheat [...] Read more.

The development of a robust Agrobacterium-mediated transformation protocol for a recalcitrant species like durum wheat requires the identification and optimization of factors affecting T-DNA delivery and plant regeneration. The purpose of this research was to compare the behavior of diverse durum wheat genotypes during in vitro culture and Agrobacterium tumefaciens-mediated transformation, using immature embryos as explants. Apart from plant genotype, two of the main influencing factors for a successful genetic transformation have been examined here, i.e., auxin source (Dicamba and 2,4-D) and duration of the pre-culture period (one, seven and 21 days). The addition of Dicamba to the media in combination with seven days pre-cultivation resulted in a general enhancement of T-DNA delivery for most of the analyzed cultivars, as revealed by β-glucuronidase (GUS) histochemical assay. Although all genotypes were able to produce calli, significant differences were detected in regeneration and transformation efficiencies, since only two (Karalis and Neolatino) out of 14 cultivars produced fertile transgenic plants. The estimated transformation efficiencies were 6.25% and 1.66% for Karalis and Neolatino, respectively, and χ² analysis revealed the stable integration and segregation of the gus transgene in T₁ and T₂ progenies. This research has demonstrated that, among the influencing factors, genotype and auxin type play the most important role in the success of durum wheat transformation. Full article

(This article belongs to the Section Natural Products Chemistry)

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7 pages, 205 KiB

Open AccessCommunication

In Vitro Antimicrobial Activity of Embothrium coccineum Used as Traditional Medicine in Patagonia against Multiresistant Bacteria

by Nicole Canales¹, Iván Montenegro², Mario Párraga³, Yusser Olguín⁴, Patricio Godoy⁵, Enrique Werner⁶ and Alejandro Madrid^7,*

¹ Escuela de Tecnología Médica Facultad de Ciencias de la Salud, Universidad Central de Chile, Edificio Gonzalo Hernández Uribe, Lord Cochrane 417, Santiago Centro 8320000, Chile

² Escuela de Obstetricia y Puericultura, Facultad de medicina, Campus de la Salud, Universidad de Valparaíso, Angamos 655, Reñaca, Viña del Mar 2520000, Chile

³ Centro de Investigaciones Biomédicas (CIB), Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda No. 2664, Valparaíso 2340000, Chile

⁴ Center for Integrative Medicine and Innovative Science (CIMIS), Facultad de Medicina, Universidad Andrés Bello, Santiago 8320000, Chile

⁵ Instituto de Microbiología Clínica, Facultad de Medicina, Universidad Austral de Chile, Los Laureles s/n, Isla Teja, Valdivia 5090000, Chile

⁶ Departamento de Ciencias Básicas, Campus Fernando May Universidad del Biobío, Avda. Andrés Bello s/n casilla 447, Chillán 3780000, Chile

⁷ Departamento de Química, Facultad de Ciencias Naturales y Exactas, Universidad de Playa Ancha, Avda. Leopoldo Carvallo 270, Playa Ancha, Valparaíso 2340000, Chile

Molecules 2016, 21(11), 1441; https://doi.org/10.3390/molecules21111441 - 31 Oct 2016

Cited by 8 | Viewed by 4677

Abstract

Embothrium coccineum J.R. Forst. & G. Forst is an evergreen tree that has been used as a folk remedy for the treatment of neuralgia, tooth pains, wound healing, and glandular conditions, as well as an antiseptic agent against bacterial infection. The antibacterial activities [...] Read more.

Embothrium coccineum J.R. Forst. & G. Forst is an evergreen tree that has been used as a folk remedy for the treatment of neuralgia, tooth pains, wound healing, and glandular conditions, as well as an antiseptic agent against bacterial infection. The antibacterial activities of sequential extracts (hexane, dichloromethane, ethyl acetate, and ethanol) from the leaves of E. coccineum were evaluated by means of the micro-dilution assay against six (Escherichia coli; Klebsiella pneumoniae; Proteus mirabilis; Pseudomonas aeruginosa; Staphylococcus aureus and Streptococcus pyogenes) multiresistant bacteria strains. Ethyl acetate extract showed the best spectra of antibacterial activity against all tested bacteria, and was analyzed by gas chromatography–mass spectrometry (GC-MS) for its composition. The results of the present work provide useful baseline information for the potential development and use of nanoparticles and/or nanofibers doped with extracts of E. coccineum in the fight against multiresistant bacteria, which would allow the validation of the traditional use of E. coccineum by native peoples of Patagonia as an antimicrobial agent in the biomedical Field. Full article

(This article belongs to the Section Natural Products Chemistry)

42 pages, 1232 KiB

Open AccessReview

Phenolic Melatonin-Related Compounds: Their Role as Chemical Protectors against Oxidative Stress

by Annia Galano^1,*, Romina Castañeda-Arriaga¹, Adriana Pérez-González²

, Dun-Xian Tan³ and Russel J. Reiter³

¹ Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa, 09340 Mexico City, Mexico

² Consejo Nacional de Ciencia y Tecnología (CONACYT)—Departamento de Química, División de Ciencias Básicas e Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco No. 186, Col. Vicentina, Iztapalapa, 09340 Mexico City, Mexico

³ Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX 78229, USA

Molecules 2016, 21(11), 1442; https://doi.org/10.3390/molecules21111442 - 29 Oct 2016

Cited by 44 | Viewed by 10309

Abstract

There is currently no doubt about the serious threat that oxidative stress (OS) poses to human health. Therefore, a crucial strategy to maintain a good health status is to identify molecules capable of offering protection against OS through chemical routes. Based on the [...] Read more.

There is currently no doubt about the serious threat that oxidative stress (OS) poses to human health. Therefore, a crucial strategy to maintain a good health status is to identify molecules capable of offering protection against OS through chemical routes. Based on the known efficiency of the phenolic and melatonin (MLT) families of compounds as antioxidants, it is logical to assume that phenolic MLT-related compounds should be (at least) equally efficient. Unfortunately, they have been less investigated than phenols, MLT and its non-phenolic metabolites in this context. The evidence reviewed here strongly suggests that MLT phenolic derivatives can act as both primary and secondary antioxidants, exerting their protection through diverse chemical routes. They all seem to be better free radical scavengers than MLT and Trolox, while some of them also surpass ascorbic acid and resveratrol. However, there are still many aspects that deserve further investigations for this kind of compounds. Full article

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

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23 pages, 6243 KiB

Open AccessCommunication

Characterisation of the Broadly-Specific O-Methyl-transferase JerF from the Late Stages of Jerangolid Biosynthesis

by Steffen Friedrich¹, Franziska Hemmerling^1,2, Frederick Lindner², Anna Warnke¹, Johannes Wunderlich², Gesche Berkhan^1,2 and Frank Hahn^1,2,*

¹ Zentrum für Biomolekulare Wirkstoffe, Leibniz-Universität Hannover, Schneiderberg 38, 30167 Hannover, Germany

² Professur für Organische Chemie (Lebensmittelchemie), Fakultät für Biologie, Chemie und Geowissenschaften, Universitätsstraße 30, 95447 Bayreuth, Germany

Molecules 2016, 21(11), 1443; https://doi.org/10.3390/molecules21111443 - 29 Oct 2016

Cited by 7 | Viewed by 7991

Abstract

We describe the characterisation of the O-methyltransferase JerF from the late stages of jerangolid biosynthesis. JerF is the first known example of an enzyme that catalyses the formation of a non-aromatic, cyclic methylenolether. The enzyme was overexpressed in E. coli and the [...] Read more.

We describe the characterisation of the O-methyltransferase JerF from the late stages of jerangolid biosynthesis. JerF is the first known example of an enzyme that catalyses the formation of a non-aromatic, cyclic methylenolether. The enzyme was overexpressed in E. coli and the cell-free extracts were used in bioconversion experiments. Chemical synthesis gave access to a series of substrate surrogates that covered a broad structural space. Enzymatic assays revealed a broad substrate tolerance and high regioselectivity of JerF, which makes it an attractive candidate for an application in chemoenzymatic synthesis with particular usefulness for late stage application on 4-methoxy-5,6-dihydro-2H-pyran-2-one-containing natural products. Full article

(This article belongs to the Special Issue Biosynthesis of Natural Products)

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13 pages, 3644 KiB

Open AccessArticle

Evidence of the Disassembly of α-Cyclodextrin-octylamine Inclusion Compounds Conjugated to Gold Nanoparticles via Thermal and Photothermal Effects

by Nataly Silva^1,2, Silvana Moris¹, Maximiliano Díaz¹, Nicolás Yutronic¹, Erika Lang³, Boris Chornik⁴, Marcelo J. Kogan^5,* and Paul Jara^1,*

¹ Department of Chemistry, Universidad of Chile, Las Palmeras 3425, Santiago 7800003, Chile

² Department of Chemistry of Materials, Universidad de Santiago de Chile, Av. Libertador Bernardo O’Higgins 3363, Santiago 9170022, Chile

³ Department of Biology, CEM, Universidad of Chile, Las Palmeras 3425, Santiago 7800003, Chile

⁴ Department of Physics, Universidad de Chile, Beauchef 850, Santiago 8370448, Chile

⁵ Department of Pharmacological and Toxicological Chemistry, Universidad of Chile, Sergio Livingston 1007, Santiago 8380492, Chile

Molecules 2016, 21(11), 1444; https://doi.org/10.3390/molecules21111444 - 29 Oct 2016

Cited by 10 | Viewed by 6466

Abstract

Cyclodextrin (CD) molecules form inclusion compounds (ICs), generating dimers that are capable of encapsulating molecules derived from long-chain hydrocarbons. The aim of this study is to evaluate the structural changes experienced by ICs in solution with increasing temperatures. For this, a nuclear magnetic [...] Read more.

Cyclodextrin (CD) molecules form inclusion compounds (ICs), generating dimers that are capable of encapsulating molecules derived from long-chain hydrocarbons. The aim of this study is to evaluate the structural changes experienced by ICs in solution with increasing temperatures. For this, a nuclear magnetic resonance (¹H-NMR) titration was performed to determinate the stoichiometric α-cyclodextrin (α-CD):octylamine (OA) 2:1 and binding constant (k = 2.16 M⁻²) of ICs. Solution samples of α-CD-OA ICs conjugated with gold nanoparticles (AuNPs) were prepared, and ¹H-NMR spectra at different temperatures were recorded. Comparatively, ¹H-NMR spectra of the sample irradiated with a laser with tunable wavelengths, with plasmons of conjugated AuNPs, were recorded. In this work, we present evidence of the disassembly of ICs conjugated with AuNPs. Thermal studies demonstrated that, at 114 °C, there are reversible rearrangements of the host and guests in the ICs in a solid state. Migration movements of the guest molecules from the CD cavity were monitored via temperature-dependent ¹H-NMR, and were verified comparing the chemical shifts of octylamine dissolved in deuterated dimethylsulfoxide (DMSO-d₆) with the OA molecule included in α-CD dissolved in the same solvent. It was observed that, at 117 °C, OA exited the α-CD cavity. CD IC dimer disassembly was also observed when the sample was irradiated with green laser light. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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17 pages, 2051 KiB

Open AccessArticle

The Effects of Pre-Fermentative Addition of Oenological Tannins on Wine Components and Sensorial Qualities of Red Wine

by Kai Chen, Carlos Escott

, Iris Loira

, Juan Manuel Del Fresno, Antonio Morata

, Wendu Tesfaye, Fernando Calderon, Santiago Benito^*

and Jose Antonio Suárez-Lepe

Chemistry and Food Technologies Department, Polytechnic University of Madrid, Avenida Complutense S/N, 28040 Madrid, Spain

Molecules 2016, 21(11), 1445; https://doi.org/10.3390/molecules21111445 - 31 Oct 2016

Cited by 38 | Viewed by 7155

Abstract

Today in the wine industry, oenological tannins are widely used to improve wine quality and prevent oxidation in wine aging. With the development of tannin products, new oenological tannins are developed with many specific functions, such as modifying antioxidant effect, colour stabilization and [...] Read more.

Today in the wine industry, oenological tannins are widely used to improve wine quality and prevent oxidation in wine aging. With the development of tannin products, new oenological tannins are developed with many specific functions, such as modifying antioxidant effect, colour stabilization and aroma modifications. The aim of this work is to investigate effects of pre-fermentative addition of oenological tannins on wine colour, anthocyanins, volatile compounds and sensorial properties. In this case, Syrah juice was extracted with classic flash thermovinification from fresh must in order to release more colour and tannins. Three types of oenological tannins, which are, respectively, derived from grape skin, seed (Vitis vinifera) and French oak (Quercus robur and Querrus petraea), were selected to carry out the experiments with seven treatments. Results indicated that tannin treatments significantly improved wine aroma complexity and sensorial properties. However, the concentration of some stable pigments such as Vitisin A, Vitisin A-Ac and Vitisin B was negatively affected by tannin additions. Nevertheless, by means of cluster analysis and principal component analysis, it was observed that higher alcohols were significantly promoted by grape seed tannin while most anthocyanins can be improved by addition of grape tannins. In conclusion, low amount of oenological tannin derived from grape seed is a promising method to be applied especially for young red wine making. Full article

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12 pages, 5723 KiB

Open AccessArticle

Urinary Metabolomic Profiling in Zucker Diabetic Fatty Rats with Type 2 Diabetes Mellitus Treated with Glimepiride, Metformin, and Their Combination

by Yu Dong^1,2, Yi-Tao Chen², Yuan-Xiao Yang², Dan Shou^1,3,* and Chang-Yu Li^2,*

¹ Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, No. 132, Tianmushan Road, Hangzhou 310007, China

² College of Pharmaceutical Science, Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou 310053, China

³ Department of Chemistry, Xixi Campus, Zhejiang University, No. 148, Tianmushan Road, Hangzhou 310028, China

Molecules 2016, 21(11), 1446; https://doi.org/10.3390/molecules21111446 - 31 Oct 2016

Cited by 22 | Viewed by 7233

Abstract

Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid [...] Read more.

Type 2 diabetes mellitus (T2DM) is a high incidence metabolic disease. Glimepiride, metformin, and their combination are the most commonly used therapeutics for T2DM in the clinic, but little is known about the metabolic responses of these therapies. In this study, ultrahigh-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-QTOF-MS)-based metabolomics was applied to detect changes in the urinary metabolomic profile of Zucker diabetic fatty (ZDF) rats in response to these treatments. Additionally, standard biochemical parameters (e.g., fasting plasma glucose, glycosylated hemoglobin, oral glucose tolerance, urinary glucose, triglyceride, total cholesterol, and insulin) and liver histopathology were monitored and observed. Six metabolites, including 3-galactosyl lactose, citric acid, sphingosine, phytosphingosine, ribothymidine, and succinoadenosine, were found significantly reverted to the normal level after these therapies. The present study is the first to present citric acid and sphinganine as the potential markers of T2DM, which could be used as indicators to observe the anti-diabetic effects of glimepiride, metformin, and their combination treatments. Full article

(This article belongs to the Section Metabolites)

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12 pages, 2255 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel 4-Morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine Derivatives Bearing Phenylpyridine/ Phenylpyrimidine-Carboxamides

by Huimin Liu¹, Wenhui Wang², Chengyu Sun^2,3, Caolin Wang², Wufu Zhu^2,* and Pengwu Zheng^2,*

¹ School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China

² School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China

³ Pharmacy Department, The Affiliated Hospital of Chongqing Three Gorges Medical College, Chongqing 404000, China

Molecules 2016, 21(11), 1447; https://doi.org/10.3390/molecules21111447 - 31 Oct 2016

Cited by 6 | Viewed by 3905

Abstract

Four series of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives 11a–j, 12a–j, 13a–g and 14a–g bearing phenylpyridine/phenylpyrimidine- carboxamide scaffolds were designed, synthesized and their IC₅₀ values against three cancer cell lines (A549, [...] Read more.

Four series of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives 11a–j, 12a–j, 13a–g and 14a–g bearing phenylpyridine/phenylpyrimidine- carboxamide scaffolds were designed, synthesized and their IC₅₀ values against three cancer cell lines (A549, PC-3 and MCF-7) were evaluated. Eleven of the compounds showed moderate cytotoxicity activity against the cancer cell lines. Structure-activity relationships (SARs) and pharmacological results indicated that the introduction of phenylpyridine-carboxamide scaffold was beneficial for the activity. What’s more, the oxidation of the sulfur atom in thiopyran and various types of substituents on the aryl group have different impacts on different series of compounds. Furthermore, the positions of aryl group substituents have a slight impact on the activity of the phenylpyridine-carboxamide series compounds. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 1472 KiB

Open AccessReview

Discovery of Bioactive Compounds by the UIC-ICBG Drug Discovery Program in the 18 Years Since 1998

by Hong-Jie Zhang^1,*,†, Wan-Fei Li^1,†, Harry H. S. Fong² and Djaja Doel Soejarto²

¹ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China

² Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1448; https://doi.org/10.3390/molecules21111448 - 31 Oct 2016

Cited by 7 | Viewed by 5798

Abstract

The International Cooperative Biodiversity Groups (ICBG) Program based at the University of Illinois at Chicago (UIC) is a program aimed to address the interdependent issues of inventory and conservation of biodiversity, drug discovery and sustained economic growth in both developing and developed countries. [...] Read more.

The International Cooperative Biodiversity Groups (ICBG) Program based at the University of Illinois at Chicago (UIC) is a program aimed to address the interdependent issues of inventory and conservation of biodiversity, drug discovery and sustained economic growth in both developing and developed countries. It is an interdisciplinary program involving the extensive synergies and collaborative efforts of botanists, chemists and biologists in the countries of Vietnam, Laos and the USA. The UIC-ICBG drug discovery efforts over the past 18 years have resulted in the collection of a cumulative total of more than 5500 plant samples (representing more than 2000 species), that were evaluated for their potential biological effects against cancer, HIV, bird flu, tuberculosis and malaria. The bioassay-guided fractionation and separation of the bioactive plant leads resulted in the isolation of approximately 300 compounds of varying degrees of structural complexity and/or biological activity. The present paper summarizes the significant drug discovery achievements made by the UIC-ICBG team of multidisciplinary collaborators in the project over the period of 1998–2012 and the projects carried on in the subsequent years by involving the researchers in Hong Kong. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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18 pages, 821 KiB

Open AccessReview

Tea Polysaccharides and Their Bioactivities

by Ling-Ling Du^1,2, Qiu-Yue Fu¹, Li-Ping Xiang², Xin-Qiang Zheng¹

, Jian-Liang Lu¹, Jian-Hui Ye¹, Qing-Sheng Li¹, Curt Anthony Polito¹ and Yue-Rong Liang^1,*

¹ Tea Research Institute, Zhejiang University, # 866 Yuhangtang Road, Hangzhou 310058, China

² National Tea and Tea product Quality Supervision and Inspection Center (Guizhou), Zunyi 563100, China

Molecules 2016, 21(11), 1449; https://doi.org/10.3390/molecules21111449 - 30 Oct 2016

Cited by 85 | Viewed by 10620

Abstract

Tea (Camellia sinensis) is a beverage beneficial to health and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of heteropolysaccharides bound with proteins. There is evidence showing [...] Read more.

Tea (Camellia sinensis) is a beverage beneficial to health and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of heteropolysaccharides bound with proteins. There is evidence showing that TPS not only improves immunity but also has various bioactivities, such as antioxidant, antitumor, antihyperglycemia, and anti-inflammation. However, inconsistent results concerning chemical composition and bioactivity of TPS have been published in recent years. The advances in chemical composition and bioactivities of TPS are reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS are also discussed. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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15 pages, 2567 KiB

Open AccessArticle

Structural Characterization and Antimicrobial Activities of 7H-Benzo[h]chromeno[2,3-d]pyrimidine and 14H-Benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c] pyrimidine Derivatives

by Rawda M. Okasha^1,*, Fawzia F. Albalawi¹, Tarek H. Afifi¹, Ahmed M. Fouda², Al-Anood M. Al-Dies²

and Ahmed M. El-Agrody³

¹ Chemistry Department, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia

² Chemistry Department, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi Arabia

³ Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt

Molecules 2016, 21(11), 1450; https://doi.org/10.3390/molecules21111450 - 1 Nov 2016

Cited by 37 | Viewed by 5745

Abstract

Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7a–o, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8a–b [...] Read more.

Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7a–o, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8a–b and 3-ethoxycarbonyl-14-(4-halophenyl)-12-methoxy-14H-benzo-[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-one derivatives 12a–b. The structure of these novel compounds were confirmed using IR, ¹H- and ¹³C-NMR as well as MS spectroscopy. The new compounds were evaluated in vitro for their antimicrobial activity and it was demonstrated that 7H-benzochromenopyrimidine and derivatives of 14H-benzochromenotriazolopyrimidine exhibited the most promising antibacterial activities compared to the reference antimicrobial agents. The structure activity relationship (SAR) studies of the target compounds agreed with the in vitro essays and confirmed higher potent antimicrobial activity against some of the tested microorganisms. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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18 pages, 3553 KiB

Open AccessFeature PaperArticle

Accumulation of Stable Full-Length Circular Group I Intron RNAs during Heat-Shock

by Kasper L. Andersen¹, Bertrand Beckert^1,2, Benoit Masquida^2,*, Steinar D. Johansen³ and Henrik Nielsen^1,*

¹ Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark

² Molecular Genetics Genomics Microbiology, Université de Strasbourg, CNRS, UMR 7156, Strasbourg 67081, France

³ Department of Medical Biology, UiT, The Arctic University of Norway, Tromsø N-9037, Norway

Molecules 2016, 21(11), 1451; https://doi.org/10.3390/molecules21111451 - 31 Oct 2016

Cited by 8 | Viewed by 7703

Abstract

Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results in formation of full-length circular introns without ligation of the exons and has been proposed to be active in intron mobility. We applied qRT-PCR [...] Read more.

Group I introns in nuclear ribosomal RNA of eukaryotic microorganisms are processed by splicing or circularization. The latter results in formation of full-length circular introns without ligation of the exons and has been proposed to be active in intron mobility. We applied qRT-PCR to estimate the copy number of circular intron RNA from the myxomycete Didymium iridis. In exponentially growing amoebae, the circular introns are nuclear and found in 70 copies per cell. During heat-shock, the circular form is up-regulated to more than 500 copies per cell. The intron harbours two ribozymes that have the potential to linearize the circle. To understand the structural features that maintain circle integrity, we performed chemical and enzymatic probing of the splicing ribozyme combined with molecular modeling to arrive at models of the inactive circular form and its active linear counterpart. We show that the two forms have the same overall structure but differ in key parts, including the catalytic core element P7 and the junctions at which reactions take place. These differences explain the relative stability of the circular species, demonstrate how it is prone to react with a target molecule for circle integration and thus supports the notion that the circular form is a biologically significant molecule possibly with a role in intron mobility. Full article

(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

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13 pages, 1753 KiB

Open AccessArticle

Anti-Inflammatory Potential of Ethyl Acetate Fraction of Moringa oleifera in Downregulating the NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated Macrophages

by Palanisamy Arulselvan^1,*, Woan Sean Tan¹, Sivapragasam Gothai¹, Katyakyini Muniandy¹, Sharida Fakurazi^1,2, Norhaizan Mohd Esa³, Abdullah A. Alarfaj⁴ and S. Suresh Kumar⁵

¹ Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

² Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

³ Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

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

⁵ Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia

Molecules 2016, 21(11), 1452; https://doi.org/10.3390/molecules21111452 - 31 Oct 2016

Cited by 63 | Viewed by 10398

Abstract

In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions [...] Read more.

In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway. Full article

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

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13 pages, 3299 KiB

Open AccessArticle

Biotransformation of Bicyclic Halolactones with a Methyl Group in the Cyclohexane Ring into Hydroxylactones and Their Biological Activity

by Katarzyna Wińska^1,*, Małgorzata Grabarczyk¹, Wanda Mączka¹, Barbara Żarowska²

, Gabriela Maciejewska³, Katarzyna Dancewicz⁴, Beata Gabryś⁴

, Antoni Szumny¹

and Mirosław Anioł¹

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

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

³ Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland

⁴ Department of Botany and Ecology, University of Zielona Gora, Szafrana 1, 65-516 Zielona Gora, Poland

Molecules 2016, 21(11), 1453; https://doi.org/10.3390/molecules21111453 - 31 Oct 2016

Cited by 10 | Viewed by 4836

Abstract

The aim of this study was the chemical synthesis of a series of halo- and unsaturated lactones, as well as their microbial transformation products. Finally some of their biological activities were assessed. Three bicyclic halolactones with a methyl group in the cyclohexane ring [...] Read more.

The aim of this study was the chemical synthesis of a series of halo- and unsaturated lactones, as well as their microbial transformation products. Finally some of their biological activities were assessed. Three bicyclic halolactones with a methyl group in the cyclohexane ring were obtained from the corresponding γ,δ-unsaturated ester during a two-step synthesis. These lactones were subjected to screening biotransformation using twenty two fungal strains. These strains were tested on their ability to transform halolactones into new hydroxylactones. Among the six strains able to catalyze hydrolytic dehalogenation, only two (Fusarium equiseti, AM22 and Yarrowia lipolytica, AM71) gave a product in a high yield. Moreover, one strain (Penicillium wermiculatum, AM30) introduced the hydroxy group on the cyclohexane ring without removing the halogen atom. The biological activity of five of the obtained lactones was tested. Some of these compounds exhibited growth inhibition against bacteria, yeasts and fungi and deterrent activity against peach-potato aphid. Full article

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16 pages, 1806 KiB

Open AccessReview

Direct Selective Oxidative Functionalization of C–H Bonds with H₂O₂: Mn-Aminopyridine Complexes Challenge the Dominance of Non-Heme Fe Catalysts

by Roman V. Ottenbacher^1,2, Evgenii P. Talsi^1,2 and Konstantin P. Bryliakov^1,2,*

¹ Chemistry Department, Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia

² Boreskov Institute of Catalysis, Pr. Lavrentieva 5, Novosibirsk 630090, Russia

Molecules 2016, 21(11), 1454; https://doi.org/10.3390/molecules21111454 - 31 Oct 2016

Cited by 34 | Viewed by 8651

Abstract

Non-heme iron(II) complexes are widespread synthetic enzyme models, capable of conducting selective C–H oxidation with H₂O₂ in the presence of carboxylic acid additives. In the last years, structurally similar manganese(II) complexes have been shown to catalyze C–H oxidation with similarly [...] Read more.

Non-heme iron(II) complexes are widespread synthetic enzyme models, capable of conducting selective C–H oxidation with H₂O₂ in the presence of carboxylic acid additives. In the last years, structurally similar manganese(II) complexes have been shown to catalyze C–H oxidation with similarly high selectivity, and with much higher efficiency. In this mini-review, recent catalytic and mechanistic data on the selective C–H oxygenations with H₂O₂ in the presence of manganese complexes are overviewed. A distinctive feature of catalyst systems of the type Mn complex/H₂O₂/carboxylic is the existence of two alternative reaction pathways (as found for the oxidation of cumenes), one leading to the formation of alcohol, and the other to ester. The mechanisms of formation of the alcohol and the ester are briefly discussed. Full article

(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)

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14 pages, 2344 KiB

Open AccessArticle

Synthesis and In Vitro Antiproliferative Activity of Novel Phenyl Ring-Substituted 5-Alkyl-12(H)-quino[3,4-b][1,4]benzothiazine Derivatives

by Andrzej Zięba^1,*, Małgorzata Latocha², Aleksander Sochanik³, Anna Nycz¹ and Dariusz Kuśmierz²

¹ Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland

² Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 9, 41-200 Sosnowiec, Poland

³ Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeże AK 15, 44-101 Gliwice, Poland

Molecules 2016, 21(11), 1455; https://doi.org/10.3390/molecules21111455 - 4 Nov 2016

Cited by 16 | Viewed by 4601

Abstract

A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group [...] Read more.

A novel series of tetracyclic quinobenzothiazine derivatives was synthetized. Compounds containing a substituent (hydroxyl, methyl, phenyl, piperidyl, or piperazinyl) in positions 9 and 11 were obtained by cyclization of suitable 4-aminoquinolinium-3-thiolates. Quinobenzothiazine 10-O-substituted derivatives were obtained by alkylating the hydroxyl group in position 10 of the parent (quinobenzothiazine) system. Antiproliferative activity of the synthesized compounds was studied using cultured neoplastic cells (MDA-MB-231, SNB-19, and C-32 cell lines). Four selected compounds were investigated in more detail for cytotoxicity and antiproliferative effect. Transcriptional activity of genes regulating cell cycle (TP53), apoptosis (BAX, BCL-2), as well as proliferation (H3) were assessed. Finally, the ability of the selected compounds to bind DNA was checked in the presence of ethidium bromide. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1722 KiB

Open AccessArticle

Heat-Killed Lactobacillus salivarius and Lactobacillus johnsonii Reduce Liver Injury Induced by Alcohol In Vitro and In Vivo

by Cheng-Hung Chuang^1,*

, Cheng-Chih Tsai², En-Shyh Lin³, Chin-Shiu Huang^4,5

, Yun-Yu Lin¹, Chuan-Ching Lan⁶ and Chun-Chih Huang⁶

¹ Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, 1018 Sec. 6 Taiwan Boulevard, Taichung 43302, Taiwan

² Department of Food Science and Technology, Hungkuang University, Taichung 43302, Taiwan

³ Department of Beauty Science, National Taichung University of Science and Technology, No. 193, Sec. 1, San-Min Rd., Taichung 40343, Taiwan

⁴ Department of Health and Nutrition Biotechnology, Asia University, 500 Lioufeng Rd., Wufeng, Taichung 41354, Taiwan

⁵ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan

⁶ New Bellus Enterprises Co., Ltd. No. 48, Industrial Rd., Erh Chen Vil., Kuan Tien Dist., Tainan 72042, Taiwan

Molecules 2016, 21(11), 1456; https://doi.org/10.3390/molecules21111456 - 31 Oct 2016

Cited by 28 | Viewed by 6830

Abstract

The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus [...] Read more.

The aim of the present study was to determine whether Lactobacillus salivarius (LS) and Lactobacillus johnsonii (LJ) prevent alcoholic liver damage in HepG2 cells and rat models of acute alcohol exposure. In this study, heat-killed LS and LJ were screened from 50 Lactobacillus strains induced by 100 mM alcohol in HepG2 cells. The severity of alcoholic liver injury was determined by measuring the levels of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (γ-GT), lipid peroxidation, triglyceride (TG) and total cholesterol. Our results indicated that heat-killed LS and LJ reduced AST, ALT, γ-GT and malondialdehyde (MDA) levels and outperformed other bacterial strains in cell line studies. We further evaluated these findings by administering these strains to rats. Only LS was able to reduce serum AST levels, which it did by 26.2%. In addition LS significantly inhibited serum TG levels by 39.2%. However, both strains were unable to inhibit ALT levels. In summary, we demonstrated that heat-killed LS and LJ possess hepatoprotective properties induced by alcohol both in vitro and in vivo. Full article

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

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9 pages, 2638 KiB

Open AccessArticle

Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity

by Yun Sun^1,2, Fenghui Sun¹, Jianlong Li¹, Minlu Wu¹, Xiang Fan³, Yanfa Meng³ and Yao Meng^1,*

¹ School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, Sichuan, China

² The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan, China

³ Key Laboratory of Bio-Resources and Eco-Environment Ministry of Education/Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Science, Sichuan University, Chengdu 610064, Sichuan, China

Molecules 2016, 21(11), 1457; https://doi.org/10.3390/molecules21111457 - 31 Oct 2016

Cited by 20 | Viewed by 6030

Abstract

PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as [...] Read more.

PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N-terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs. Full article

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

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10 pages, 1816 KiB

Open AccessArticle

Developing HIV-1 Protease Inhibitors through Stereospecific Reactions in Protein Crystals

by Folasade M. Olajuyigbe^1,2,†, Nicola Demitri^1,3,†

, Rita De Zorzi¹ and Silvano Geremia^1,*

¹ Centre of Excellence in Biocrystallography, Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste 34127, Italy

² Department of Biochemistry, School of Sciences, Federal University of Technology Akure, P.M.B. 704, Akure 340252, Ondo State, Nigeria

³ Elettra-Sincrotrone Trieste, S.S. 14 Km 163.5 in Area Science Park, Basovizza, Trieste 34149, Italy

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1458; https://doi.org/10.3390/molecules21111458 - 31 Oct 2016

Viewed by 6552

Abstract

Protease inhibitors are key components in the chemotherapy of HIV infection. However, the appearance of viral mutants routinely compromises their clinical efficacy, creating a constant need for new and more potent inhibitors. Recently, a new class of epoxide-based inhibitors of HIV-1 protease was [...] Read more.

Protease inhibitors are key components in the chemotherapy of HIV infection. However, the appearance of viral mutants routinely compromises their clinical efficacy, creating a constant need for new and more potent inhibitors. Recently, a new class of epoxide-based inhibitors of HIV-1 protease was investigated and the configuration of the epoxide carbons was demonstrated to play a crucial role in determining the binding affinity. Here we report the comparison between three crystal structures at near-atomic resolution of HIV-1 protease in complex with the epoxide-based inhibitor, revealing an in-situ epoxide ring opening triggered by a pH change in the mother solution of the crystal. Increased pH in the crystal allows a stereospecific nucleophile attack of an ammonia molecule onto an epoxide carbon, with formation of a new inhibitor containing amino-alcohol functions. The described experiments open a pathway for the development of new stereospecific protease inhibitors from a reactive lead compound. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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13 pages, 2741 KiB

Open AccessArticle

Phylogenetic and Diversity Analysis of Dactylis glomerata Subspecies Using SSR and IT-ISJ Markers

by Defei Yan, Xinxin Zhao, Yajuan Cheng, Xiao Ma, Linkai Huang^*

and Xinquan Zhang^*

Department of Grassland Science, Animal Science and Technology College, Sichuan Agricultural University, Chengdu 611130, China

Molecules 2016, 21(11), 1459; https://doi.org/10.3390/molecules21111459 - 31 Oct 2016

Cited by 8 | Viewed by 4967

Abstract

The genus Dactylis, an important forage crop, has a wide geographical distribution in temperate regions. While this genus is thought to include a single species, Dactylis glomerata, this species encompasses many subspecies whose relationships have not been fully characterized. In this [...] Read more.

The genus Dactylis, an important forage crop, has a wide geographical distribution in temperate regions. While this genus is thought to include a single species, Dactylis glomerata, this species encompasses many subspecies whose relationships have not been fully characterized. In this study, the genetic diversity and phylogenetic relationships of nine representative Dactylis subspecies were examined using SSR and IT-ISJ markers. In total, 21 pairs of SSR primers and 15 pairs of IT-ISJ primers were used to amplify 295 polymorphic bands with polymorphic rates of 100%. The average polymorphic information contents (PICs) of SSR and IT-ISJ markers were 0.909 and 0.780, respectively. The combined data of the two markers indicated a high level of genetic diversity among the nine D. glomerata subspecies, with a Nei’s gene diversity index value of 0.283 and Shannon’s diversity of 0.448. Preliminarily phylogenetic analysis results revealed that the 20 accessions could be divided into three groups (A, B, C). Furthermore, they could be divided into five clusters, which is similar to the structure analysis with K = 5. Phylogenetic placement in these three groups may be related to the distribution ranges and the climate types of the subspecies in each group. Group A contained eight accessions of four subspecies, originating from the west Mediterranean, while Group B contained seven accessions of three subspecies, originating from the east Mediterranean. Full article

(This article belongs to the Section Molecular Diversity)

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16 pages, 3669 KiB

Open AccessArticle

Red Light Activation of Ru(II) Polypyridyl Prodrugs via Triplet-Triplet Annihilation Upconversion: Feasibility in Air and through Meat

by Sven H. C. Askes, Michael S. Meijer, Tessel Bouwens, Iris Landman and Sylvestre Bonnet^*

Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, Leiden 2333 CC, The Netherlands

Molecules 2016, 21(11), 1460; https://doi.org/10.3390/molecules21111460 - 1 Nov 2016

Cited by 30 | Viewed by 6763

Abstract

Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed [...] Read more.

Triplet-triplet annihilation upconversion (TTA-UC) is a promising photophysical tool to shift the activation wavelength of photopharmacological compounds to the red or near-infrared wavelength domain, in which light penetrates human tissue optimally. However, TTA-UC is sensitive to dioxygen, which quenches the triplet states needed for upconversion. Here, we demonstrate not only that the sensitivity of TTA-UC liposomes to dioxygen can be circumvented by adding antioxidants, but also that this strategy is compatible with the activation of ruthenium-based chemotherapeutic compounds. First, red-to-blue upconverting liposomes were functionalized with a blue-light sensitive, membrane-anchored ruthenium polypyridyl complex, and put in solution in presence of a cocktail of antioxidants composed of ascorbic acid and glutathione. Upon red light irradiation with a medical grade 630 nm PDT laser, enough blue light was produced by TTA-UC liposomes under air to efficiently trigger full activation of the Ru-based prodrug. Then, the blue light generated by TTA-UC liposomes under red light irradiation (630 nm, 0.57 W/cm²) through different thicknesses of pork or chicken meat was measured, showing that TTA-UC still occurred even beyond 10 mm of biological tissue. Overall, the rate of activation of the ruthenium compound in TTA-UC liposomes using either blue or red light (1.6 W/cm²) through 7 mm of pork fillet were found comparable, but the blue light caused significant tissue damage, whereas red light did not. Finally, full activation of the ruthenium prodrug in TTA-UC liposomes was obtained under red light irradiation through 7 mm of pork fillet, thereby underlining the in vivo applicability of the activation-by-upconversion strategy. Full article

(This article belongs to the Special Issue Photoresponsive Drugs)

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10 pages, 380 KiB

Open AccessArticle

Chemical Constituents of Muehlenbeckia tamnifolia (Kunth) Meisn (Polygonaceae) and Its In Vitro α-Amilase and α-Glucosidase Inhibitory Activities

by María Torres-Naranjo¹, Alirica Suárez^2,3, Gianluca Gilardoni¹

, Luis Cartuche¹, Paola Flores¹ and Vladimir Morocho^1,*

¹ Departamento de Química, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador

² Facultad de Farmacia, Universidad Central de Venezuela, Caracas 1040, Venezuela

³ Prometeo Project Researcher, SENESCYT, Quito 170516, Ecuador

Molecules 2016, 21(11), 1461; https://doi.org/10.3390/molecules21111461 - 2 Nov 2016

Cited by 78 | Viewed by 7894

Abstract

The phytochemical investigation of Muehlenbeckia tamnifolia, collected in Loja-Ecuador, led to the isolation of nine known compounds identified as: lupeol acetate (1); cis-p-coumaric acid (2); lupeol (3); β-sitosterol (4) trans- [...] Read more.

The phytochemical investigation of Muehlenbeckia tamnifolia, collected in Loja-Ecuador, led to the isolation of nine known compounds identified as: lupeol acetate (1); cis-p-coumaric acid (2); lupeol (3); β-sitosterol (4) trans-p-coumaric acid (5); linoleic acid (6) (+)-catechin (7); afzelin (8) and quercitrin (9). The structures of the isolated compounds were determined based on analysis of NMR and MS data, as well as comparison with the literature. The hypoglycemic activity of crude extracts and isolated compounds was assessed by the ability to inhibit α-amylase and α-glucosidase enzymes. The hexane extract showed weak inhibitory activity on α-amylase, with an IC₅₀ value of 625 µg·mL⁻¹, while the other extracts and isolated compounds were inactive at the maximum dose tested. The results on α-glucosidase showed more favorable effects; the hexanic and methanolic extracts exhibited a strong inhibitory activity with IC₅₀ values of 48.22 µg·mL⁻¹ and 19.22 µg·mL⁻¹, respectively. Four of the nine isolated compounds exhibited strong inhibitory activity with IC₅₀ values below 8 µM, much higher than acarbose (377 uM). Linoleic acid was the most potent compound (IC₅₀ = 0.42 µM) followed by afzelin, (+)-catechin and quercitrin. Full article

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14 pages, 5564 KiB

Open AccessArticle

Novel Selective and Potent EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer

by Yanxia Li^1,2, Zhendong Song³, Yue Jin³, Zeyao Tang³, Jian Kang^1,* and Xiaodong Ma^3,*

¹ Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China

² Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China

³ College of Pharmacy, Dalian Medical University, Dalian 116044, Liaoning Province, China

Molecules 2016, 21(11), 1462; https://doi.org/10.3390/molecules21111462 - 2 Nov 2016

Cited by 13 | Viewed by 7737

Abstract

Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this [...] Read more.

Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this study, we report the novel molecule N-(3-((5-chloro-2-(4-((1-morpholino)methyl)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (DY3002) to preferentially inhibit the EGFR T790M mutant (EGFR^T790M) (IC₅₀ = 0.71 nM) over wild-type EGFR (IC₅₀ = 448.7 nM) in kinase assays. Compared to rociletinib (SI = 21.4) and osimertinib (SI = 40.9), it significantly increased selectivity (SI = 632.0) against EGFR^T790M over wild-type EGFR. Furthermore, in cell-based tests, DY3002, with an IC₅₀ value of 0.037 μM, exhibited enhanced inhibitory potency against H1975 cells. Moreover, AO/EB and DAPI staining assays as well as flow cytometer analyses indicated that DY3002 possesses superior biological properties compared to alternatives. In addition, a rat oral glucose tolerance test revealed that treatment with high drug doses (50 mg/kg) of DY3002 did not result in hyperglycemia, suggesting a reduction of side effects in NSCLC patients will be achievable relative to established EGFR inhibitors. In summary, our findings indicate DY3002 as a promising preclinical candidate for effective treatment of patients with EGFR^T790M-mutated NSCLC. Full article

(This article belongs to the Special Issue Kinase Inhibitor Chemistry)

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0 pages, 148 KiB

Open AccessRetraction

RETRACTED: Lee et al. The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1. Molecules 2016, 21, 594

by Dong-Sung Lee¹, Tae-Gyu Nam², Byeong-Seon Jeong^3,* and Gil-Saeng Jeong^4,*

¹ College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea

² Department of Pharmacy, Hanyang University, Ansan 15588, Korea

³ College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea

⁴ College of Pharmacy, Keimyung University, Daegu 42601, Korea

Molecules 2016, 21(11), 1463; https://doi.org/10.3390/molecules21111463 - 7 Nov 2016

Viewed by 4254

Abstract

As the authors of the title paper [...]
Full article

10 pages, 205 KiB

Open AccessArticle

LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics

by Rohit H. Budhraja¹, Milin A. Shah¹, Mahendra Suthar¹, Arun Yadav¹, Sahil P. Shah¹, Prashant Kale^1,2, Parisa Asvadi³, Mariadhas Valan Arasu⁴, Naif Abdullah Al-Dhabi⁴, Chun Geon Park⁵, Young-Ock Kim^5,*, Hak Jae Kim^6,*, Y. K. Agrawal² and Ravi. K. Krovidi^1,*

¹ Panomics Lambda Therapeutic Research Limited, Gota, Ahmedabad, Gujarat 382481, India

² Department of Pharmaceutical Sciences, Gujarat Forensic Sciences University, Gandhinagar 382481, India

³ Analytical Development and Global Regulatory Affairs, Intas Pharmaceuticals Ltd., Ahmedabad, Gujarat 382213, India

⁴ Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

⁵ Department of Medicinal Crop Research, Rural Development Administration, Eumseong, Chungbuk 369-873, Korea

⁶ Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea

Molecules 2016, 21(11), 1464; https://doi.org/10.3390/molecules21111464 - 2 Nov 2016

Cited by 14 | Viewed by 6663

Abstract

Quantitative targeted proteomics based approaches deploy state-of-the-art Liquid chromatography tandem mass spectrometry LC-MS technologies and are evolving as a complementary technique to standard ligand-binding based assays. Advancements in MS technology, which have augmented the specificity, selectivity and sensitivity limits of detection and freedom [...] Read more.

Quantitative targeted proteomics based approaches deploy state-of-the-art Liquid chromatography tandem mass spectrometry LC-MS technologies and are evolving as a complementary technique to standard ligand-binding based assays. Advancements in MS technology, which have augmented the specificity, selectivity and sensitivity limits of detection and freedom from antibody generation, have made it amicable towards various clinical applications. In our current work, a surrogate peptide based quantitative proteomics assessment is performed by selecting specific signature peptides from the complementary determining region CDR region of trastuzumab (Herclon^®, Roche products in India). We developed a double Stable Isotope Label (dSIL) approach by using two different surrogate peptides to evaluate the proteolytic digestion efficiency and accurate quantification of the target analyte peptide of Herclon^® in human serum. Method validation experiments were meticulously performed as per bioanalytical method validation guidelines. The dSIL approach, using an LC-MS/MS based quantification assay demonstrated good linearity over a range of 5–500 µg/mL of Herclon^®, and validation experimental data is in compliance with bioanalytical regulatory guidelines. Full article

11 pages, 4601 KiB

Open AccessArticle

Cytotoxic, Antitumor and Immunomodulatory Effects of the Water-Soluble Polysaccharides from Lotus (Nelumbo nucifera Gaertn.) Seeds

by Yafeng Zheng¹, Qi Wang^1,2, Weijing Zhuang¹, Xu Lu¹, Anca Miron³

, Tsun-Thai Chai⁴

, Baodong Zheng^1,*

and Jianbo Xiao^5,*

¹ College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China

² Institute of Agricultural Engineering, Fujian Academy of Agriculture Sciences, Fuzhou 350003, China

³ Faculty of Pharmacy, Grigore T. Popa University of Medicine and Pharmacy Iasi, Universitatii Street, No. 16, Iasi 700115, Romania

⁴ Department of Chemical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Jalan Universiti Bandar Barat, Kampar 31900, Perak, Malaysia

⁵ Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau, China

Molecules 2016, 21(11), 1465; https://doi.org/10.3390/molecules21111465 - 2 Nov 2016

Cited by 30 | Viewed by 9614

Abstract

Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water–soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant [...] Read more.

Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water–soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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11 pages, 2578 KiB

Open AccessArticle

Application of Homochiral Alkylated Organic Cages as Chiral Stationary Phases for Molecular Separations by Capillary Gas Chromatography

by Shengming Xie, Junhui Zhang

, Nan Fu, Bangjin Wang, Cong Hu and Liming Yuan^*

Department of Chemistry, Yunnan Normal University, Kunming 650500, China

Molecules 2016, 21(11), 1466; https://doi.org/10.3390/molecules21111466 - 8 Nov 2016

Cited by 18 | Viewed by 6635

Abstract

Molecular organic cage compounds have attracted considerable attention due to their potential applications in gas storage, catalysis, chemical sensing, molecular separations, etc. In this study, a homochiral pentyl cage compound was synthesized from a condensation reaction of (S,S)-1,2-pentyl-1,2-diaminoethane and [...] Read more.

Molecular organic cage compounds have attracted considerable attention due to their potential applications in gas storage, catalysis, chemical sensing, molecular separations, etc. In this study, a homochiral pentyl cage compound was synthesized from a condensation reaction of (S,S)-1,2-pentyl-1,2-diaminoethane and 1,3,5-triformylbenzene. The imine-linked pentyl cage diluted with a polysiloxane (OV-1701) was explored as a novel stationary phase for high-resolution gas chromatographic separation of organic compounds. Some positional isomers were baseline separated on the pentyl cage-coated capillary column. In particular, various types of enantiomers including chiral alcohols, esters, ethers and epoxides can be resolved without derivatization on the pentyl cage-coated capillary column. The reproducibility of the pentyl cage-coated capillary column for separation was investigated using nitrochlorobenzene and styrene oxide as analytes. The results indicate that the column has good stability and separation reproducibility after being repeatedly used. This work demonstrates that molecular organic cage compounds could become a novel class of chiral separation media in the near future. Full article

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

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6 pages, 2730 KiB

Open AccessCommunication

Preparation of Cu@Cu₂O Nanocatalysts by Reduction of HKUST-1 for Oxidation Reaction of Catechol

by Seongwan Jang^1,†, Chohye Yoon^1,†, Jae Myung Lee², Sungkyun Park^3,* and Kang Hyun Park^1,*

¹ Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-765, Korea

² Department of Naval Architecture & Ocean Engineering, Pusan National University, Busan 609-735, Korea

³ Department of Physics, Pusan National University, Busan 609-735, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1467; https://doi.org/10.3390/molecules21111467 - 2 Nov 2016

Cited by 9 | Viewed by 7174

Abstract

HKUST-1, a copper-based metal organic framework (MOF), has been investigated as a catalyst in various reactions. However, the HKUST-1 shows low catalytic activity in the oxidation of catechol. Therefore, we synthesized Fe₃O₄@HKUST-1 by layer-by layer assembly strategy and Cu@Cu [...] Read more.

HKUST-1, a copper-based metal organic framework (MOF), has been investigated as a catalyst in various reactions. However, the HKUST-1 shows low catalytic activity in the oxidation of catechol. Therefore, we synthesized Fe₃O₄@HKUST-1 by layer-by layer assembly strategy and Cu@Cu₂O by reduction of HKUST-1 for enhancement of catalytic activity. Cu@Cu₂O nanoparticles exhibited highly effective catalytic activity in oxidation of 3,5-di-tert-butylcatechol. Through this method, MOF can maintain the original core-shell structure and be used in various other reactions with enhanced catalytic activity. Full article

(This article belongs to the Special Issue Metal Nanocatalysts in Green Synthesis and Energy Applications)

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19 pages, 1119 KiB

Open AccessReview

Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis

by Souvik Banerjee^†, Dong-Jin Hwang^†, Wei Li^*

and Duane D. Miller^*

¹ Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave. Memphis, TN 38163, USA

^† These authors contributed equally.

Molecules 2016, 21(11), 1468; https://doi.org/10.3390/molecules21111468 - 2 Nov 2016

Cited by 50 | Viewed by 11114

Abstract

Extensive research over the last decade has resulted in a number of highly potent tubulin polymerization inhibitors acting either as microtubule stabilizing agents (MSAs) or microtubule destabilizing agents (MDAs). These inhibitors have potent cytotoxicity against a broad spectrum of human tumor cell lines. [...] Read more.

Extensive research over the last decade has resulted in a number of highly potent tubulin polymerization inhibitors acting either as microtubule stabilizing agents (MSAs) or microtubule destabilizing agents (MDAs). These inhibitors have potent cytotoxicity against a broad spectrum of human tumor cell lines. In addition to cytotoxicity, a number of these tubulin inhibitors have exhibited abilities to inhibit formation of new blood vessels as well as disrupt existing blood vessels. Tubulin inhibitors as a vascular disrupting agents (VDAs), mainly from the MDA family, induce rapid tumor vessel occlusion and massive tumor necrosis. Thus, tubulin inhibitors have become increasingly popular in the field of tumor vasculature. However, their pharmaceutical application is halted by a number of limitations including poor solubility and toxicity. Thus, recently, there has been considerable interests in the nanoparticle drug delivery of tubulin inhibitors to circumvent those limitations. This article reviews recent advances in nanoparticle based drug delivery for tubulin inhibitors as well as their tumor vasculature disruption properties. Full article

(This article belongs to the Special Issue Tubulin Inhibitors)

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12 pages, 7376 KiB

Open AccessArticle

Bauhinia championii Flavone Attenuates Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes by Improving Mitochondrial Dysfunction

by Ping Liao^1,†, Guibo Sun^2,†, Chan Zhang¹, Min Wang², Yao Sun¹, Yuehan Zhou¹, Xiaobo Sun^2,* and Jie Jian^1,*

¹ Department of Pharmacology, Guilin Medical University, Huan Cheng North 2nd Road, Guilin 541004, Guangxi, China

² Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1469; https://doi.org/10.3390/molecules21111469 - 4 Nov 2016

Cited by 17 | Viewed by 7663

Abstract

This study aimed to determine the effects of Bauhinia championii flavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation. [...] Read more.

This study aimed to determine the effects of Bauhinia championii flavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation. Cell viability was detected by CCK-8 assay. Apoptotic rate was measured by Annexin V/PI staining. Levels of mitochondria-associated ROS, mitochondrial transmembrane potential (∆Ψm) and mitochondrial permeability transition pores (MPTP) opening were assessed by fluorescent probes. ATP production was measured by ATP assay kit. The release of cytochrome c, translocation of Bax, and related proteins were measured by western blotting. Our results showed that pretreatment with BCF significantly improved cell viability and attenuated the cardiomyocyte apoptosis caused by H/R. Furthermore, BCF increased ATP production and inhibited ROS-generating mitochondria, depolarization of ΔΨm, and MPTP opening. Moreover, BCF pretreatment decreased Bax mitochondrial translocation, cytochrome c release, and activation of caspase-3, as well as increased the expression of p-PI3K, p-Akt, and the ratio of Bcl-2 to Bax. Interestingly, a specific inhibitor of phosphatidylinositol 3-kinase, LY294002, partly reversed the anti-apoptotic effect of BCF. These observations indicated that BCF pretreatment attenuates H/R-induced myocardial apoptosis strength by improving mitochondrial dysfunction via PI3K/Akt signaling pathway. Full article

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12 pages, 5416 KiB

Open AccessArticle

In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells

by Subramaniyan Bharathiraja¹, Hansu Seo², Panchanathan Manivasagan¹, Madhappan Santha Moorthy¹, Suhyun Park³ and Jungwan Oh^1,2,*

¹ Marine-Integrated Bionics Research Center, Pukyong National University, Busan 608-737, Korea

² Department of Biomedical Engineering and Center for Marine-Integrated Biotechnology (BK21 Plus), Pukyong National University, Busan 608-737, Korea

³ Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA

Molecules 2016, 21(11), 1470; https://doi.org/10.3390/molecules21111470 - 3 Nov 2016

Cited by 71 | Viewed by 9883

Abstract

C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It [...] Read more.

C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy. Full article

(This article belongs to the Special Issue Photodynamic Therapy)

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13 pages, 9323 KiB

Open AccessArticle

Rapid Screening and Identification of BSA Bound Ligands from Radix astragali Using BSA Immobilized Magnetic Nanoparticles Coupled with HPLC-MS

by Liangliang Liu¹, Juan Leng¹, Xiai Yang¹, Liping Liao¹, Yin Cen³, Aiping Xiao^1,* and Lei Ma^2,*

¹ Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China

² State Key Laboratory of Cotton Biology, Institute of Cotton Research of CAAS, Anyang 455000, China

³ College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China

Molecules 2016, 21(11), 1471; https://doi.org/10.3390/molecules21111471 - 5 Nov 2016

Cited by 18 | Viewed by 5591

Abstract

Radix astragali is widely used either as a single herb or as a collection of herbs in a complex prescription in China. In this study, bovine serum albumin functionalized magnetic nanoparticles (BSA-MN) coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) were used to [...] Read more.

Radix astragali is widely used either as a single herb or as a collection of herbs in a complex prescription in China. In this study, bovine serum albumin functionalized magnetic nanoparticles (BSA-MN) coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) were used to screen and identify bound ligands from the n-butanol part of a Radix astragali extract. The prepared BSA-MN showed sufficient magnetic response for the separation with an ordinary magnet and satisfied reusability. Fundamental parameters affecting the preparation of BSA-MN and the screening efficiency were studied and optimized. Under the optimum conditions, four bound ligands were screened out from the n-butanol part of a Radix astragali extract and identified as genistin (1), calycosin-7-O-β-d-glucoside (2), ononin (3) and formononetin (4). This effective method could be widely applied for rapid screening and identification of active compounds from complex mixtures without the need for preparative isolation. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 1077 KiB

Open AccessArticle

Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety

by Cédric Spitz

, Fanny Mathias, Alain Gamal Giuglio-Tonolo, Thierry Terme and Patrice Vanelle^*

Aix-Marseille Université, CNRS, ICR UMR 7273, Equipe Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille CEDEX 05, France

Molecules 2016, 21(11), 1472; https://doi.org/10.3390/molecules21111472 - 4 Nov 2016

Cited by 2 | Viewed by 4278

Abstract

We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine [...] Read more.

We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl–protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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11 pages, 1001 KiB

Open AccessArticle

Synthesis and Formulation of Thermosensitive Drug Carrier for Temperature Triggered Delivery of Naproxen Sodium

by Monika Gasztych, Agnieszka Gola

, Justyna Kobryń and Witold Musiał^*

Department of Physical Chemistry, Pharmaceutical Faculty, Wroclaw Medical University, Borowska 211, Wroclaw 50-556, Poland

Molecules 2016, 21(11), 1473; https://doi.org/10.3390/molecules21111473 - 4 Nov 2016

Cited by 11 | Viewed by 5512

Abstract

Nanospheres and microspheres are known as a multipurpose compounds and are used in various branches of science. Recent controlled delivery systems for drugs are also based on poly-micro and nanospheres. In our study we describe an investigation of the influence of thermosensitive polymer [...] Read more.

Nanospheres and microspheres are known as a multipurpose compounds and are used in various branches of science. Recent controlled delivery systems for drugs are also based on poly-micro and nanospheres. In our study we describe an investigation of the influence of thermosensitive polymer N-isopropylacrylamide (NIPA) on the release of the drug naproxen sodium (NS) with a hydrogel hydroxypropyl methylcellulose (HPMC) base. The hydrodynamic diameter (D_H) of the obtained polymer was measured by using dynamic light scattering (DLS) at a wavelength of 678 nm. Hydrogel formulations of NS were prepared in a specific way ex tempore. NS was sprinkled on the surface of a distilled water, then polymer soluted in water was added. Afterward, HPMC was affixed to the solution. Prepared samples were stored at room temperature for 24 h. Release tests showed that modification of thevcross-linker type influenced the properties of synthesized polymeric particles. The NIPA derivatives obtained via surfactant free precipitation polymerization (SFPP) may be formulated as hydrogel preparations using HPMC. The obtained formulations presented varied half-release times, depending on the type of applied NIPA derivatives in hydrogel formulations. At 18 °C, the release rates were lower comparing to the reference HPMC hydrogel, whereas at 42 °C, the release rates were significantly higher. The synthesized thermosensitive polymers enabled temperature-triggered release of NS. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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26 pages, 6143 KiB

Open AccessReview

Synthetic Procedures Leading towards Aminobisphosphonates

by Ewa Chmielewska^*

and Paweł Kafarski

Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław 50-370, Poland

Molecules 2016, 21(11), 1474; https://doi.org/10.3390/molecules21111474 - 4 Nov 2016

Cited by 34 | Viewed by 11226

Abstract

Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used [...] Read more.

Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents. Full article

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

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12 pages, 2295 KiB

Open AccessArticle

Effects of Light Intensity on the Growth, Photosynthetic Characteristics, and Flavonoid Content of Epimedium pseudowushanense B.L.Guo

by Junqian Pan

and Baolin Guo^*

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China

Molecules 2016, 21(11), 1475; https://doi.org/10.3390/molecules21111475 - 4 Nov 2016

Cited by 54 | Viewed by 9275

Abstract

Epimedium pseudowushanense B.L.Guo is used in traditional medicine as an aphrodisiac and to strengthen muscles and bones. Several recent reports have shown that flavonoids from Epimedium also significantly affect the treatment of breast cancer, liver cancer, and leukemia. However, few studies have examined [...] Read more.

Epimedium pseudowushanense B.L.Guo is used in traditional medicine as an aphrodisiac and to strengthen muscles and bones. Several recent reports have shown that flavonoids from Epimedium also significantly affect the treatment of breast cancer, liver cancer, and leukemia. However, few studies have examined the medicinal-ingredient yield of Epimedium, a light-demanding shade herb, under different light intensities. To investigate the effects of light intensity on medicinal-ingredient yields, Epimedium was exposed to five levels of light intensity until harvest time. Leaf dry biomass under L4 was the highest among different light treatments. L4 was also associated with the highest net photosynthetic rate. Quantification of epimedin A, epimedin B, epimedin C, and icariin showed that L3 produced the highest amount of epimedin C, and that flavonoid content responded to light levels differently. Results indicated that L3 and L4 were the optimal light levels for medicinal-ingredient yield. Full article

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14 pages, 587 KiB

Open AccessArticle

Assessment of Chemical Impact of Invasive Bryozoan Pectinatella magnifica on the Environment: Cytotoxicity and Antimicrobial Activity of P. magnifica Extracts

by Peter Kollar^1,*, Karel Šmejkal², Hana Salmonová³

, Eva Vlková³, Olga Lepšová-Skácelová⁴, Zuzana Balounová⁵, Josef Rajchard⁵, Josef Cvačka⁶

, Libor Jaša^7,8, Pavel Babica^7,8

and Jiří Pazourek⁹

¹ Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého tř. 1946/1, Brno 61242, Czech Republic

² Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého tř. 1946/1, Brno 61242, Czech Republic

³ Department of Microbiology, Nutrition and Dietetics, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Kamýcká 129, Prague 6, 16521, Czech Republic

⁴ Department of Botany, Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 31, České Budějovice 37005, Czech Republic

⁵ Department of Biological Studies, Faculty of Agriculture, University of South Bohemia in České Budějovice, Studentská 13, České Budějovice 37005, Czech Republic

⁶ Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, Prague 16610, Czech Republic

⁷ RECETOX—Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 60200, Czech Republic

⁸ Department of Experimental Phycology and Ecotoxicology, Institute of Botany, Academy of Sciences of the Czech Republic, Lidická 25/27, Brno 60200, Czech Republic

⁹ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého tř. 1946/1, Brno 61242, Czech Republic

Molecules 2016, 21(11), 1476; https://doi.org/10.3390/molecules21111476 - 4 Nov 2016

Cited by 7 | Viewed by 7330

Abstract

Pectinatella magnifica, an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal [...] Read more.

Pectinatella magnifica, an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal on the environment. In this paper, we aimed to evaluate in vitro cytotoxic effects of five extracts prepared from P. magnifica using LDH assay on THP-1 cell line. Antimicrobial activities of extracts against 22 different bacterial strains were tested by microdilution method. Our study showed that all extracts tested, except aqueous portion, demonstrated LD₅₀ values below 100 μg/mL, which indicates potential toxicity. The water extract of P. magnifica with LD₅₀ value of 250 μg/mL also shows potentially harmful effects. Also, an environmental risk resulting from the presence and increasing biomass of potentially toxic benthic cyanobacteria in old colonies should not be underestimated. Toxicity of Pectinatella extracts could be partially caused by presence of Aeromonas species in material, since we found members of these genera as most abundant bacteria associated with P. magnifica. Furthermore, P. magnifica seems to be a promising source of certain antimicrobial agents. Its methanolic extract, hexane, and chloroform fractions possessed selective inhibitory effect on some potential pathogens and food spoiling bacteria in the range of MIC 0.5–10 mg/mL. Future effort should be made to isolate and characterize the content compounds derived from P. magnifica, which could help to identify the substance(s) responsible for the toxic effects of P. magnifica extracts. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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16 pages, 246 KiB

Open AccessArticle

Statistical Significance of the Maximum Hardness Principle Applied to Some Selected Chemical Reactions

by Ranajit Saha, Sudip Pan and Pratim K. Chattaraj^*

Department of Chemistry and Centre for Theoretical Studies, Indian Institute of Technology Kharagpur, Kharagpur 721302, India

Molecules 2016, 21(11), 1477; https://doi.org/10.3390/molecules21111477 - 5 Nov 2016

Cited by 7 | Viewed by 5265

Abstract

The validity of the maximum hardness principle (MHP) is tested in the cases of 50 chemical reactions, most of which are organic in nature and exhibit anomeric effect. To explore the effect of the level of theory on the validity of MHP in [...] Read more.

The validity of the maximum hardness principle (MHP) is tested in the cases of 50 chemical reactions, most of which are organic in nature and exhibit anomeric effect. To explore the effect of the level of theory on the validity of MHP in an exothermic reaction, B3LYP/6-311++G(2df,3pd) and LC-BLYP/6-311++G(2df,3pd) (def2-QZVP for iodine and mercury) levels are employed. Different approximations like the geometric mean of hardness and combined hardness are considered in case there are multiple reactants and/or products. It is observed that, based on the geometric mean of hardness, while 82% of the studied reactions obey the MHP at the B3LYP level, 84% of the reactions follow this rule at the LC-BLYP level. Most of the reactions possess the hardest species on the product side. A 50% null hypothesis is rejected at a 1% level of significance. Full article

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

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15 pages, 3917 KiB

Open AccessArticle

“Miswak” Based Green Synthesis of Silver Nanoparticles: Evaluation and Comparison of Their Microbicidal Activities with the Chemical Synthesis

by Mohammed Rafi Shaik¹

, Ghadeer H. Albalawi^1,2, Shams Tabrez Khan³, Merajuddin Khan¹, Syed Farooq Adil¹

, Mufsir Kuniyil¹

, Abdulrahman Al-Warthan¹, Mohammed Rafiq H. Siddiqui¹

, Hamad Z. Alkhathlan^1,* and Mujeeb Khan^1,*

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

² Faculty of Science, University of Tabuk, P.O. Box 741, Tabuk 71491, Saudi Arabia

³ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2016, 21(11), 1478; https://doi.org/10.3390/molecules21111478 - 6 Nov 2016

Cited by 45 | Viewed by 10345

Abstract

Microbicidal potential of silver nanoparticles (Ag-NPs) can be drastically improved by improving their solubility or wettability in the aqueous medium. In the present study, we report the synthesis of both green and chemical synthesis of Ag-NPs, and evaluate the effect of the dispersion [...] Read more.

Microbicidal potential of silver nanoparticles (Ag-NPs) can be drastically improved by improving their solubility or wettability in the aqueous medium. In the present study, we report the synthesis of both green and chemical synthesis of Ag-NPs, and evaluate the effect of the dispersion qualities of as-prepared Ag-NPs from both methods on their antimicrobial activities. The green synthesis of Ag-NPs is carried out by using an aqueous solution of readily available Salvadora persica L. root extract (RE) as a bioreductant. The formation of highly crystalline Ag-NPs was established by various analytical and microscopic techniques. The rich phenolic contents of S. persica L. RE (Miswak) not only promoted the reduction and formation of NPs but they also facilitated the stabilization of the Ag-NPs, which was established by Fourier transform infrared spectroscopy (FT-IR) analysis. Furthermore, the influence of the volume of the RE on the size and the dispersion qualities of the NPs was also evaluated. It was revealed that with increasing the volume of RE the size of the NPs was deteriorated, whereas at lower concentrations of RE smaller size and less aggregated NPs were obtained. During this study, the antimicrobial activities of both chemically and green synthesized Ag-NPs, along with the aqueous RE of S. persica L., were evaluated against various microorganisms. It was observed that the green synthesized Ag-NPs exhibit comparable or slightly higher antibacterial activities than the chemically obtained Ag-NPs. Full article

(This article belongs to the Section Green Chemistry)

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17 pages, 8440 KiB

Open AccessArticle

Medium Optimization and Fermentation Kinetics for κ-Carrageenase Production by Thalassospira sp. Fjfst-332

by Juanjuan Guo^1,2, Longtao Zhang^1,2, Xu Lu¹, Shaoxiao Zeng¹, Yi Zhang¹, Hui Xu¹ and Baodong Zheng^1,*

¹ College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350000, Fujian, China

² Fujian Provincial Technical Research Center of Marine Food and Biological Products Processing, Fujian Agriculture and Forestry University, Fuzhou 350000, Fujian, China

Molecules 2016, 21(11), 1479; https://doi.org/10.3390/molecules21111479 - 5 Nov 2016

Cited by 17 | Viewed by 6454

Abstract

Effective degradation of κ-carrageenan by isolated Thalassospira sp. fjfst-332 is reported for the first time in this paper. It was identified by 16S rDNA sequencing and morphological observation using Transmission Electron Microscopy (TEM). Based on a Plackett–Burman design for significant variables, Box–Behnken experimental [...] Read more.

Effective degradation of κ-carrageenan by isolated Thalassospira sp. fjfst-332 is reported for the first time in this paper. It was identified by 16S rDNA sequencing and morphological observation using Transmission Electron Microscopy (TEM). Based on a Plackett–Burman design for significant variables, Box–Behnken experimental design and response surface methodology were used to optimize the culture conditions. Through statistical optimization, the optimum medium components were determined as follows: 2.0 g/L κ-carrageenan, 1.0 g/L yeast extract, 1.0 g/L FOS, 20.0 g/L NaCl, 2.0 g/L NaNO₃, 0.5 g/L MgSO₄·7H₂O, 0.1 g/L K₂HPO₄, and 0.1 g/L CaCl₂. The highest activity exhibited by Thalassospira sp. fjfst-332 was 267 U/mL, which makes it the most vigorous wild bacterium for κ-carrageenan production. In order to guide scaled-up production, two empirical models—the logistic equation and Luedeking–Piretequation—were proposed to predict the strain growth and enzyme production, respectively. Furthermore, we report the fermentation kinetics and every empirical equation of the coefficients (α, β, X₀, X_m and μ_m) for the two models, which could be used to design and optimize industrial processes. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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20 pages, 4866 KiB

Open AccessArticle

Comparative Analysis of the Effects of Hydroxysafflor Yellow A and Anhydrosafflor Yellow B in Safflower Series of Herb Pairs Using Prep-HPLC and a Selective Knock-Out Approach

by Cheng Qu^1,†, Lin-Yan Wang^1,†, Wen-Tao Jin², Yu-Ping Tang^1,*

, Yi Jin¹, Xu-Qin Shi¹, Li-Li Shang¹, Er-Xin Shang¹ and Jin-Ao Duan¹

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China

² No. 29 High School, Nanjing 210036, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1480; https://doi.org/10.3390/molecules21111480 - 6 Nov 2016

Cited by 21 | Viewed by 6611

Abstract

The flower of Carthamus tinctorius L. (Carthami Flos, safflower), important in traditional Chinese medicine (TCM), is known for treating blood stasis, coronary heart disease, hypertension, and cerebrovascular disease in clinical and experimental studies. It is widely accepted that hydroxysafflor yellow A (HSYA) and [...] Read more.

The flower of Carthamus tinctorius L. (Carthami Flos, safflower), important in traditional Chinese medicine (TCM), is known for treating blood stasis, coronary heart disease, hypertension, and cerebrovascular disease in clinical and experimental studies. It is widely accepted that hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (ASYB) are the major bioactive components of many formulae comprised of safflower. In this study, selective knock-out of target components such as HSYA and ASYB by using preparative high performance liquid chromatography (prep-HPLC) followed by antiplatelet and anticoagulation activities evaluation was used to investigate the roles of bioactive ingredients in safflower series of herb pairs. The results showed that both HSYA and ASYB not only played a direct role in activating blood circulation, but also indirectly made a contribution to the total bioactivity of safflower series of herb pairs. The degree of contribution of HSYA in the safflower and its series herb pairs was as follows: Carthami Flos-Ginseng Radix et Rhizoma Rubra (CF-GR) > Carthami Flos-Sappan Lignum (CF-SL) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Astragali Radix (CF-AR) > Carthami Flos-Angelicae Sinensis Radix (CF-AS) > Carthami Flos-Glycyrrhizae Radix et Rhizoma (CF-GL) > Carthami Flos-Salviae Miltiorrhizae Radix et Rhizoma (CF-SM) > Carthami Flos (CF), and the contribution degree of ASYB in the safflower and its series herb pairs: CF-GL > CF-PS > CF-AS > CF-SL > CF-SM > CF-AR > CF-GR > CF. So, this study provided a significant and effective approach to elucidate the contribution of different herbal components to the bioactivity of the herb pair, and clarification of the variation of herb-pair compatibilities. In addition, this study provides guidance for investigating the relationship between herbal compounds and the bioactivities of herb pairs. It also provides a scientific basis for reasonable clinical applications and new drug development on the basis of the safflower series of herb pairs. Full article

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7 pages, 718 KiB

Open AccessArticle

Triterpenoids from Ainsliaea yunnanensis Franch. and Their Biological Activities

by Jinjie Li^1,2

, Bo Zhang², Hailing Liu¹, Xuan Zhang¹, Xiaoya Shang^2,* and Changqi Zhao^1,*

¹ Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing 100875, China

² Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China

Molecules 2016, 21(11), 1481; https://doi.org/10.3390/molecules21111481 - 7 Nov 2016

Cited by 14 | Viewed by 4666

Abstract

One new pentacyclic triterpenoid, 3β-carboxylicfilic-4(23)-ene (1), and three known pentacyclic triterpenoids, adian-5-en-3α-ol (2), fernenol (3), and fern-7-en-3β-ol (4) were isolated from the petroleum ether phase of the ethanolic extract of Ainsliaea yunnanensis Franch. Their structures [...] Read more.

One new pentacyclic triterpenoid, 3β-carboxylicfilic-4(23)-ene (1), and three known pentacyclic triterpenoids, adian-5-en-3α-ol (2), fernenol (3), and fern-7-en-3β-ol (4) were isolated from the petroleum ether phase of the ethanolic extract of Ainsliaea yunnanensis Franch. Their structures were established by spectroscopic methods including 1-D and 2-D NMR, and MS experiments. Compounds 1, 2, 3, and 4 showed significant selective cytotoxicity against human acute monocytic leukemia cell line (THP-1) with IC₅₀ values of 5.12 μM, 1.78 μM, 1.74 μM, and 1.75 μΜ, respectively. Compound 1 also showed an anti-inflammatory effect through the inhibition of the activity of NF-κB by blocking the nuclear translocation of p65. Full article

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17 pages, 3370 KiB

Open AccessReview

Water and Aqueous Mixtures as Convenient Alternative Media for Organoselenium Chemistry

by Claudio Santi^1,*

, Raquel G. Jacob², Bonifacio Monti¹, Luana Bagnoli¹

, Luca Sancineto¹ and Eder J. Lenardão²

¹ Department of Pharmaceutical Sciences, Group of Catalysis and Organic Green Chemistry, University of Perugia, Via del Liceo 1, Perugia 06100, Italy

² Laboratório de Síntese Orgânica Limpa-LASOL-CCQFA-Universidade Federal de Pelotas-UFPel, P.O. Box 354, Pelotas 96010-900, RS, Brazil

Molecules 2016, 21(11), 1482; https://doi.org/10.3390/molecules21111482 - 6 Nov 2016

Cited by 35 | Viewed by 7750

Abstract

Even if water is the natural environment for bioorganic reactions, its use in organic chemistry is often severely limited by the high insolubility of the organic derivatives. In this review, we introduce some examples of the use of water to perform organoselenium chemistry. [...] Read more.

Even if water is the natural environment for bioorganic reactions, its use in organic chemistry is often severely limited by the high insolubility of the organic derivatives. In this review, we introduce some examples of the use of water to perform organoselenium chemistry. We mainly discuss the advantages of this medium when the recyclability is demonstrated and when the water can control the selectivity of a reaction or enhance the reaction rate. Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

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12 pages, 1580 KiB

Open AccessArticle

Synthesis and In Vitro Anti Leishmania amazonensis Biological Screening of Morita-Baylis-Hillman Adducts Prepared from Eugenol, Thymol and Carvacrol

by Francisco José Seixas Xavier¹, Klinger Antonio da Franca Rodrigues²

, Ramon Guerra De Oliveira¹, Claudio Gabriel Lima Junior¹, Juliana Da Câmara Rocha³, Tatjana Souza Lima Keesen³, Marcia Rosa De Oliveira², Fábio Pedrosa Lins Silva^1,* and Mário Luiz Araújo de Almeida Vasconcellos^1,*

¹ Laboratório de Síntese Orgânica Medicinal da Paraíba (LASOM-PB), Departamento de Química, Universidade Federal da Paraíba, Campus I, João Pessoa, Paraíba CEP 58059-900, Brazil

² Programa de Pós-graduação em Biologia Molecular and Departamento de Biologia Molecular, Centro de Ciências Exatas and da Natureza, Universidade Federal da Paraíba, João Pessoa, Paraíba CEP 58059-900, Brazil

³ Departamento de Biotecnologia, Universidade Federal da Paraíba, Campus I, João Pessoa, Paraíba CEP 58059-900, Brazil

Molecules 2016, 21(11), 1483; https://doi.org/10.3390/molecules21111483 - 8 Nov 2016

Cited by 22 | Viewed by 5700

Abstract

Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes [...] Read more.

Leishmaniasis represents a series of severe neglected tropical diseases caused by protozoa of the genus Leishmania and is widely distributed around the world. Here, we present the syntheses of Morita-Baylis-Hillman adducts (MBHAs) prepared from eugenol, thymol and carvacrol, and their bioevaluation against promastigotes of Leishmania amazonensis. The new MBHAs are prepared in two steps from essential oils in moderate to good yields and present IC₅₀ values in the range of 22.30–4.71 μM. Moreover, the selectivity index to the most potent compound is very high (SIrb > 84.92), far better than that of Glucantime^® (SIrb 1.39) and amphotericin B (SIrb = 22.34). Conformational analysis were carried out at the M062X//6-31+G(d,p) level of theory to corroborate a hypothesis about the nitroaromatic bioreduction mechanism. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1708 KiB

Open AccessArticle

Enantioseparation Using Cellulose Tris(3,5-dimethylphenylcarbamate) as Chiral Stationary Phase for HPLC: Influence of Molecular Weight of Cellulose

by Yuji Okada¹, Chiyo Yamamoto¹, Masami Kamigaito¹, Yuan Gao², Jun Shen^2,* and Yoshio Okamoto^1,2,*

¹ Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan

² Polymer Materials Research Center, Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China

Molecules 2016, 21(11), 1484; https://doi.org/10.3390/molecules21111484 - 8 Nov 2016

Cited by 24 | Viewed by 6812

Abstract

The cellulose oligomers with different degrees of polymerization (DP), 7, 11, 18, 24, 26, 40 and 52, were prepared by hydrolysis of microcrystalline cellulose with phosphoric acid. These oligomers including the starting microcrystalline cellulose (DP 124) were converted to tris(3,5-dimethylphenylcarbamate) (CDMPC) derivatives by [...] Read more.

The cellulose oligomers with different degrees of polymerization (DP), 7, 11, 18, 24, 26, 40 and 52, were prepared by hydrolysis of microcrystalline cellulose with phosphoric acid. These oligomers including the starting microcrystalline cellulose (DP 124) were converted to tris(3,5-dimethylphenylcarbamate) (CDMPC) derivatives by the reaction with an excess of 3,5-dimethylphenyl isocyanate to be used as the chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC). The structures of the CDMPC derivatives were investigated by infrared spectroscopy (IR), ¹H-NMR, circular dichroism (CD) and size exclusion chromatography (SEC), and the DPs of the derivatives estimated by SEC agreed with those estimated by ¹H-NMR. After coating the derivatives on silica gel, their chiral recognition abilities were evaluated using eight racemates under a normal phase condition with a hexane-2-propanol (99/1) mixture as an eluent. The chiral recognition abilities of 7- and 11-mers, particularly the former, were lower than those of the higher oligomers from DP 18 to 52, which had rather similar abilities to that of 124-mer, although the abilities depended on the racemates. DP 18 seems to be sufficient for CDMPC to exhibit chiral recognition similar to that of the CDMPC with larger DPs. Full article

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

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12 pages, 1464 KiB

Open AccessArticle

Aroma Release in Wine Using Co-Immobilized Enzyme Aggregates

by Katherine Ahumada¹

, Ana Martínez-Gil², Yerko Moreno-Simunovic², Andrés Illanes¹ and Lorena Wilson^1,*

¹ School of Biochemical Engineering, Pontificia Universidad Católica de Valparaíso, Valparaíso 2362803, Chile

² Technological Center for Grapevine and Wine, Faculty of Agricultural Sciences, Universidad de Talca, Talca 824000, Chile

Molecules 2016, 21(11), 1485; https://doi.org/10.3390/molecules21111485 - 8 Nov 2016

Cited by 28 | Viewed by 6750

Abstract

Aroma is a remarkable factor of quality and consumer preference in wine, representing a distinctive feature of the product. Most aromatic compounds in varietals are in the form of glycosidic precursors, which are constituted by a volatile aglycone moiety linked to a glucose [...] Read more.

Aroma is a remarkable factor of quality and consumer preference in wine, representing a distinctive feature of the product. Most aromatic compounds in varietals are in the form of glycosidic precursors, which are constituted by a volatile aglycone moiety linked to a glucose residue by an O-glycosidic bond; glucose is often linked to another sugar (arabinose, rhamnose or apiose). The use of soluble β-glycosidases for aroma liberation implies the addition of a precipitating agent to remove it from the product and precludes its reuse after one batch. An attractive option from a technological perspective that will aid in removing such constraints is the use of immobilized glycosidases. Immobilization by aggregation and crosslinking is a simple strategy producing enzyme catalysts of very high specific activity, being an attractive option to conventional immobilization to solid inert supports. The purpose of this work was the evaluation of co-immobilized β-glycosidases crosslinked aggregates produced from the commercial preparation AR2000, which contains the enzymes involved in the release of aromatic terpenes in Muscat wine (α-l-arabinofuranosidase and β-d-glucopyranosidase). To do so, experiments were conducted with co-immobilized crosslinked enzyme aggregates (combi-CLEAs), and with the soluble enzymes, using an experiment without enzyme addition as control. Stability of the enzymes at the conditions of winemaking was assessed and the volatiles composition of wine was determined by SPE-GC-MS. Stability of enzymes in combi-CLEAs was much higher than in soluble form, 80% of the initial activity remaining after 60 days in contact with the wine; at the same conditions, the soluble enzymes had lost 80% of their initial activities after 20 days. Such higher stabilities will allow prolonged use of the enzyme catalyst reducing its impact in the cost of winemaking. Wine treated with combi-CLEAs was the one exhibiting the highest concentration of total terpenes (18% higher than the control) and the highest concentrations of linalool (20% higher), nerol (20% higher) and geraniol (100% higher), which are the most important terpenes in determining Muscat typicity. Co-immobilized enzymes were highly stable at winemaking conditions, so their reutilization is possible and technologically attractive by reducing the impact of enzyme cost on winemaking cost. Full article

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

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11 pages, 3711 KiB

Open AccessArticle

Proteomic Analysis of Tung Tree (Vernicia fordii) Oilseeds during the Developmental Stages

by Zhiyong Zhan^1,2,3,†, Yicun Chen^1,2,†, Jay Shockey⁴, Xiaojiao Han^1,2 and Yangdong Wang^1,2,*

¹ State Key Laboratory of Tree Genetics and Breeding, Chinese Academy of Forestry, Beijing 100091, China

² Research Institute of Subtropical Foresty, Chinese Academy of Forestry, Fuyang 311400, Zhejiang, China

³ Jiangxi Academy of Forestry, Nanchang 330013, Jiangxi, China

⁴ United States Department of Agriculture-Agricultural Research Service, Southern Regional Research Center, New Orleans, LA 70124, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1486; https://doi.org/10.3390/molecules21111486 - 8 Nov 2016

Cited by 11 | Viewed by 5781

Abstract

The tung tree (Vernicia fordii), a non-model woody plant belonging to the Euphorbiaceae family, is a promising economic plant due to the high content of a novel high-value oil in its seeds. Many metabolic pathways are active during seed development. Oil [...] Read more.

The tung tree (Vernicia fordii), a non-model woody plant belonging to the Euphorbiaceae family, is a promising economic plant due to the high content of a novel high-value oil in its seeds. Many metabolic pathways are active during seed development. Oil (triacylglycerols (TAGs)) accumulates in oil bodies distributed in the endosperm cells of tung tree seeds. The relationship between oil bodies and oil content during tung tree seed development was analyzed using ultrastructural observations, which confirmed that oil accumulation was correlated with the volumes and numbers of oil bodies in the endosperm cells during three different developmental stages. For a deeper understanding of seed development, we carried out proteomic analyses. At least 144 proteins were differentially expressed during three different developmental stages. A total of 76 proteins were successfully identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry/mass spectrometry (MALDI-TOF/MS/MS). These proteins were grouped into 11 classes according to their functions. The major groups of differentially expressed proteins were associated with energy metabolism (25%), fatty acid metabolism (15.79%) and defense (14.47%). These results strongly suggested that a very high percentage of gene expression in seed development is dedicated to the synthesis and accumulation of TAGs. Full article

(This article belongs to the Section Bioorganic Chemistry)

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14 pages, 2305 KiB

Open AccessArticle

Synthesis of Optically Active Poly(diphenylacetylene)s Using Polymer Reactions and an Evaluation of Their Chiral Recognition Abilities as Chiral Stationary Phases for HPLC

by Katsuhiro Maeda^*, Miyuki Maruta, Yuki Sakai, Tomoyuki Ikai and Shigeyoshi Kanoh

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan

Molecules 2016, 21(11), 1487; https://doi.org/10.3390/molecules21111487 - 7 Nov 2016

Cited by 40 | Viewed by 8505

Abstract

A series of optically active poly(diphenylacetylene) derivatives bearing a chiral substituent (poly-2S) or chiral and achiral substituents (poly-(2S_x-co-3_1−x)) on all of their pendant phenyl rings were synthesized by the reaction of [...] Read more.

A series of optically active poly(diphenylacetylene) derivatives bearing a chiral substituent (poly-2S) or chiral and achiral substituents (poly-(2S_x-co-3_1−x)) on all of their pendant phenyl rings were synthesized by the reaction of poly(bis(4-carboxyphenyl)acetylene) with (S)-1-phenylethylamine ((S)-2) or benzylamine (3) in the presence of a condensing reagent. Their chiroptical properties and chiral recognition abilities as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) were investigated. Poly-2S and poly-(2S_x-co-3_1−x) (0.06 < x < 0.71) formed a preferred-handed helical conformation with opposite helical senses after thermal annealing despite possessing the same chiral pendant (h-poly-2S and h-poly-(2S_x-co-3_1−x)). Furthermore, h-poly-2S and h-poly-(2S_0.36-co-3_0.64) emitted circularly polarized luminescence with opposite signs. h-Poly-2S showed higher chiral recognition abilities toward a larger number of racemates than poly-2S without a preferred-handed helicity and the previously reported preferred-handed poly(diphenylacetylene) derivative bearing the same chiral substituent on half of its pendant phenyl rings. h-Poly-(2S_0.36-co-3_0.64) also exhibited good chiral recognition abilities toward several racemates, though the elution order of some enantiomers was reversed compared with h-poly-2S. Full article

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

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11 pages, 913 KiB

Open AccessArticle

Synthesis and Pharmacological Evaluation of Novel Pleuromutilin Derivatives with Substituted Benzimidazole Moieties

by Xin Ai¹, Xiuying Pu², Yunpeng Yi¹, Yu Liu¹, Shuijin Xu³, Jianping Liang¹ and Ruofeng Shang^1,*

¹ Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, 335 Jiangouyan, Lanzhou 730050, China

² College of Life Science and Engineering, Lanzhou University of Technology, 287 Langongping Road, Lanzhou 730050, China

³ Yancheng Shunbao Chemical Co., Ltd., Yancheng 224555, China

Molecules 2016, 21(11), 1488; https://doi.org/10.3390/molecules21111488 - 8 Nov 2016

Cited by 11 | Viewed by 4831

Abstract

A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their [...] Read more.

A series of novel pleuromutilin derivatives with substituted benzimidazole moieties were designed and synthesized from pleuromutilin and 5-amino-2-mercaptobenzimidazole through sequential reactions. All the newly synthesized compounds were characterized by IR, NMR, and HRMS. Each of the derivatives was evaluated in vitro for their antibacterial activity against Escherichia coli (E. coli) and five Gram (+) inoculums. 14-O-((5-amino-benzimidazole-2-yl) thioacetyl) mutilin (3) was the most active compound and showed highest antibacterial activities. Furthermore, we evaluated the inhibition activities of compound 3 on short-term S. aureus and MRSA growth and cytochrome P450 (CYP). The bioassay results indicate that compound 3 could be considered potential antibacterial agents but with intermediate inhibition of CYP3A4. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 1695 KiB

Open AccessArticle

The Cooperative Effect of Genistein and Protein Hydrolysates on the Proliferation and Survival of Osteoblastic Cells (hFOB 1.19)

by Shuo Wang¹, Yu Fu^1,2,3 and Xin-Huai Zhao^1,2,*

¹ Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, 150030 Harbin, China

² Department of Food Science, Northeast Agricultural University, 150030 Harbin, China

³ Department of Food Science, Aarhus University, Blichers Allé 20, 8830 Tjele, Denmark

Molecules 2016, 21(11), 1489; https://doi.org/10.3390/molecules21111489 - 8 Nov 2016

Cited by 10 | Viewed by 4942

Abstract

Chum salmon skin gelatin, de-isoflavoned soy protein, and casein were hydrolyzed at two degrees of hydrolysis. Genistein, the prepared hydrolysates, and genistein-hydrolysate combinations were assessed for their proliferative and anti-apoptotic effects on human osteoblasts (hFOB 1.19) to clarify potential cooperative effects between genistein [...] Read more.

Chum salmon skin gelatin, de-isoflavoned soy protein, and casein were hydrolyzed at two degrees of hydrolysis. Genistein, the prepared hydrolysates, and genistein-hydrolysate combinations were assessed for their proliferative and anti-apoptotic effects on human osteoblasts (hFOB 1.19) to clarify potential cooperative effects between genistein and these hydrolysates in these two activities. Genistein at 2.5 μg/L demonstrated the highest proliferative activity, while the higher dose of genistein inhibited cell growth. All hydrolysates promoted osteoblast proliferation by increasing cell viability to 102.9%–131.1%. Regarding etoposide- or NaF-induced osteoblast apoptosis, these hydrolysates at 0.05 g/L showed both preventive and therapeutic effects against apoptosis. In the mode of apoptotic prevention, the hydrolysates decreased apoptotic cells from 32.9% to 15.2%–23.7% (etoposide treatment) or from 23.6% to 14.3%–19.6% (NaF treatment). In the mode of apoptotic rescue, the hydrolysates lessened the extent of apoptotic cells from 15.9% to 13.0%–15.3% (etoposide treatment) or from 13.3% to 10.9%–12.7% (NaF treatment). Gelatin hydrolysates showed the highest activities among all hydrolysates in all cases. All investigated combinations (especially the genistein-gelatin hydrolysate combination) had stronger proliferation, apoptotic prevention, and rescue than genistein itself or their counterpart hydrolysates alone, suggesting that genistein cooperated with these hydrolysates, rendering greater activities in osteoblast proliferation and anti-apoptosis. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3938 KiB

Open AccessArticle

Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury

by Peng Sun^1,2,†, Shun-Zong Song^1,†, Shuang Jiang¹, Xia Li¹, You-Li Yao¹, Yan-Ling Wu¹, Li-Hua Lian^1,* and Ji-Xing Nan^1,2,*

¹ Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China

² Clinical Research Center, Yanbian University Hospital, Yanji 133002, China

^† These authors contribute equally to this work.

Molecules 2016, 21(11), 1490; https://doi.org/10.3390/molecules21111490 - 9 Nov 2016

Cited by 48 | Viewed by 8672

Abstract

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like [...] Read more.

The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion and mRNA expression of of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 2310 KiB

Open AccessArticle

Catalytic Oxidation of NO over MnO_x–CeO₂ and MnO_x–TiO₂ Catalysts

by Xiaolan Zeng, Xiaoyue Huo, Tianle Zhu^*, Xiaowei Hong and Ye Sun

School of Space and Environment, Beihang University, Beijing 100191, China

Molecules 2016, 21(11), 1491; https://doi.org/10.3390/molecules21111491 - 14 Nov 2016

Cited by 20 | Viewed by 7006

Abstract

A series of MnO_x–CeO₂ and MnO_x–TiO₂ catalysts were prepared by a homogeneous precipitation method and their catalytic activities for the NO oxidation in the absence or presence of SO₂ were evaluated. Results show that the optimal [...] Read more.

A series of MnO_x–CeO₂ and MnO_x–TiO₂ catalysts were prepared by a homogeneous precipitation method and their catalytic activities for the NO oxidation in the absence or presence of SO₂ were evaluated. Results show that the optimal molar ratio of Mn/Ce and Mn/Ti are 0.7 and 0.5, respectively. The MnO_x–CeO₂ catalyst exhibits higher catalytic activity and better resistance to SO₂ poisoning than the MnO_x–TiO₂ catalyst. On the basis of Brunauer–Emmett–Teller (BET), X-ray diffraction (XRD), and scanning transmission electron microscope with mapping (STEM-mapping) analyses, it is seen that the MnO_x–CeO₂ catalyst possesses higher BET surface area and better dispersion of MnO_x over the catalyst than MnO_x–TiO₂ catalyst. X-ray photoelectron spectroscopy (XPS) measurements reveal that MnO_x–CeO₂ catalyst provides the abundance of Mn³⁺ and more surface adsorbed oxygen, and SO₂ might be preferentially adsorbed to the surface of CeO₂ to form sulfate species, which provides a protection of MnO_x active sites from being poisoned. In contrast, MnO_x active sites over the MnO_x–TiO₂ catalyst are easily and quickly sulfated, leading to rapid deactivation of the catalyst for NO oxidation. Furthermore, temperature programmed desorption with NO and O₂ (NO + O₂-TPD) and in situ diffuse reflectance infrared transform spectroscopy (in situ DRIFTS) characterizations results show that the MnO_x–CeO₂ catalyst displays much stronger ability to adsorb NO_x than the MnO_x–TiO₂ catalyst, especially after SO₂ poisoning. Full article

(This article belongs to the Special Issue Transition Metal Catalysis 2016)

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13 pages, 1759 KiB

Open AccessReview

Inflammasomes and Natural Ingredients towards New Anti-Inflammatory Agents

by Patrick Dutartre

Laboratory BioperoxIL, Faculty of Sciences SVTE, University of Bourgogne Franche Comté, 6 Bd Gabriel F-21000 Dijon, France

Molecules 2016, 21(11), 1492; https://doi.org/10.3390/molecules21111492 - 8 Nov 2016

Cited by 15 | Viewed by 7221

Abstract

Inflammasomes are a family of proteins in charge of the initiation of inflammatory process during innate immune response. They are now considered major actors in many chronic inflammatory diseases. However, no major drug focusing on this target is currently on the market. Among [...] Read more.

Inflammasomes are a family of proteins in charge of the initiation of inflammatory process during innate immune response. They are now considered major actors in many chronic inflammatory diseases. However, no major drug focusing on this target is currently on the market. Among the various approaches aiming to control this major metabolic pathway, compounds aiming to modify the intracellular antioxidant profile appear to be promising. This can be obtained by “light” antioxidants able to induce natural antioxidant response of the cell itself. This review will give an overview of the current available information on this promising pharmacology approach. Full article

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

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10 pages, 1093 KiB

Open AccessArticle

A Stereocontrolled Protocol to Highly Functionalized Fluorinated Scaffolds through a Fluoride Opening of Oxiranes

by Attila Márió Remete¹, Melinda Nonn², Santos Fustero³, Ferenc Fülöp^1,2

and Loránd Kiss^1,*

¹ Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary

² MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, Eötvös u. 6, H-6720 Szeged, Hungary

³ Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Valencia, Av. Vicente Andrés Estellés, s/n 46100 Valencia, Spain

Molecules 2016, 21(11), 1493; https://doi.org/10.3390/molecules21111493 - 17 Nov 2016

Cited by 12 | Viewed by 5235

Abstract

A novel selective and substrate-dependent synthetic protocol has been developed towards the synthesis of various fluorine-containing, highly functionalized cycloalkane derivatives. The method involves the stereoselective epoxidation of some unsaturated cyclic β-amino acid derivatives as model compounds, followed by a regioselective fluoride opening of [...] Read more.

A novel selective and substrate-dependent synthetic protocol has been developed towards the synthesis of various fluorine-containing, highly functionalized cycloalkane derivatives. The method involves the stereoselective epoxidation of some unsaturated cyclic β-amino acid derivatives as model compounds, followed by a regioselective fluoride opening of oxiranes under various conditions with Deoxofluor and XtalFluor-E reagents, thereby offering an insight into this new epoxide opening methodology with fluoride. Full article

(This article belongs to the Special Issue Fluorine Chemistry 2016)

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21 pages, 6485 KiB

Open AccessReview

Structural Characterization of Flavonoid Glycoconjugates and Their Derivatives with Mass Spectrometric Techniques

by Piotr Kachlicki¹

, Anna Piasecka^1,2, Maciej Stobiecki² and Łukasz Marczak^2,*

¹ Institute of Plant Genetics, Polish Academy of Sciences, Strzeszyńska 34, 60-479 Poznań, Poland

² Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland

Molecules 2016, 21(11), 1494; https://doi.org/10.3390/molecules21111494 - 8 Nov 2016

Cited by 130 | Viewed by 13132

Abstract

Mass spectrometry is currently one of the most versatile and sensitive instrumental methods applied to structural characterization of plant secondary metabolite mixtures isolated from biological material including flavonoid glycoconjugates. Resolution of the applied mass spectrometers plays an important role in structural studies of [...] Read more.

Mass spectrometry is currently one of the most versatile and sensitive instrumental methods applied to structural characterization of plant secondary metabolite mixtures isolated from biological material including flavonoid glycoconjugates. Resolution of the applied mass spectrometers plays an important role in structural studies of mixtures of the target compounds isolated from biological material. High-resolution analyzers allow obtaining information about elemental composition of the analyzed compounds. Application of various mass spectrometric techniques, including different systems of ionization, analysis of both positive and negative ions of flavonoids, fragmentation of the protonated/deprotonated molecules and in some cases addition of metal ions to the studied compounds before ionization and fragmentation, may improve structural characterization of natural products. In our review we present different strategies allowing structural characterization of positional isomers and isobaric compounds existing in class of flavonoid glycoconjugates and their derivatives, which are synthetized in plants and are important components of the human food and drugs as well as animal feed. Full article

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

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11 pages, 2288 KiB

Open AccessArticle

Feasibility of Fraction Collection in HPLC Systems with Evaporative Light Scattering Detector: Analysis of Pectinatella magnifica

by Jiří Pazourek^1,*

and Karel Šmejkal²

¹ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého tr. 1946/1, Brno 61242, Czech Republic

² Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého tr. 1946/1, Brno 61242, Czech Republic

Molecules 2016, 21(11), 1495; https://doi.org/10.3390/molecules21111495 - 8 Nov 2016

Cited by 2 | Viewed by 6310

Abstract

The use of a liquid chromatography (LC) splitter inserted between an HPLC column and an evaporative light scattering detector (ELSD) is described. This paper aims to show the feasibility of using the splitter in an HPLC-ELSD system to fractionate a model mixture of [...] Read more.

The use of a liquid chromatography (LC) splitter inserted between an HPLC column and an evaporative light scattering detector (ELSD) is described. This paper aims to show the feasibility of using the splitter in an HPLC-ELSD system to fractionate a model mixture of analytes, namely salicin (2-(hydroxymethyl)-phenyl-β-d-glucopyranoside) and glucose. The retention factors and efficiency of the separation were studied under various temperatures and water contents in the mobile phase in order to clarify the mechanism of polyols separation on a diol column under the conditions of hydrophilic liquid chromatography (HILIC). Finally, the system was applied to a biological sample (a lyophilized colony gel of Pectinatella magnifica), where the presence of fructose and glucose was confirmed. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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14 pages, 5733 KiB

Open AccessArticle

Sugar Composition Analysis of Fuzi Polysaccharides by HPLC-MSⁿ and Their Protective Effects on Schwann Cells Exposed to High Glucose

by Bei-Bei Wang^1,†, Jia-Li Wang^1,†, Jiang Yuan¹, Qing-Hua Quan¹, Rui-Fang Ji¹, Peng Tan¹, Jing Han^2,* and Yong-Gang Liu^1,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Wangjing Zhonghuan Road No. 6 School Range, Chaoyang District, Beijing 100102, China

² Beijing Chinese Medicine Research Institute, Beijing University of Chinese Medicine, North Third Ring Road No. 11 School Range, Chaoyang District, Beijing 100029, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1496; https://doi.org/10.3390/molecules21111496 - 9 Nov 2016

Cited by 29 | Viewed by 7171

Abstract

Fuzi has been used to treat diabetic complications for many years in china. In a previous study, we have shown that Fuzi aqueous extract can attenuate Diabetic peripheral neuropathy (DPN) in rats and protect Schwann cells from injury. Thus, the protective effect of [...] Read more.

Fuzi has been used to treat diabetic complications for many years in china. In a previous study, we have shown that Fuzi aqueous extract can attenuate Diabetic peripheral neuropathy (DPN) in rats and protect Schwann cells from injury. Thus, the protective effect of Fuzi polysaccharides (FPS) on high glucose-induced SCs and the preliminary mechanism were investigated. Firstly, the FPS were obtained and their monose composition was analyzed by the combination of pre-column derivatization and high performance liquid chromatography coupled with electrospray ionization multi-tandem mass spectrometry (HPLC/ESI-MSⁿ). The results witnessed the efficiency of this method and seven monosaccharides were tentatively identified, among which fucose was first reported. Simultaneously, m/z 215 can be considered as diagnostic ions to confirm the number of monosaccharides. Next, high glucose-induced SC model was applied and divided into model group, treated group of FPS, normal and osmotic control group. After treatment for 48 h, the data showed FPS could significantly decrease the intracellular ROS and apoptosis, which were determined by the corresponding fluorescent probes. Then, the expression of oxidative stress-related proteins in SCs were measured by Western blot. Furthermore, the protein tests found that FPS markedly up-regulated superoxide dismutase (SOD), catalase (CAT) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein level, but down-regulated NADPH oxidase-1 (Nox1) protein level. Moreover, FPS could also increase AMP-activated protein kinase (AMPK) activation significantly. Hence, we preliminary deduced that AMPK-PGC-1α pathway may play an important role in the protective effect of FPS against high glucose-induced cell damage. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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19 pages, 1267 KiB

Open AccessArticle

A Modular Synthetic Approach to Isosteric Sulfonic Acid Analogues of the Anticoagulant Pentasaccharide Idraparinux

by Erika Mező, Dániel Eszenyi, Eszter Varga, Mihály Herczeg and Anikó Borbás^*

Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary

Molecules 2016, 21(11), 1497; https://doi.org/10.3390/molecules21111497 - 11 Nov 2016

Cited by 6 | Viewed by 5686

Abstract

Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we [...] Read more.

Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied. Full article

(This article belongs to the Collection Advances in Glycosciences)

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20 pages, 9050 KiB

Open AccessArticle

Large Scale Screening of Southern African Plant Extracts for the Green Synthesis of Gold Nanoparticles Using Microtitre-Plate Method

by Abdulrahman M. Elbagory¹, Christopher N. Cupido^2,3, Mervin Meyer¹ and Ahmed A. Hussein^4,*,†

¹ DST/Mintek Nanotechnology Innovation Centre, Department of Biotechnology, University of the Western Cape, Private Bag X17, Bellville 7530, South Africa

² South African National Biodiversity Institute, Compton Herbarium, Private bag X7, Claremont 7735, South Africa

³ Department of Biodiversity and Conservation Biology, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa

⁴ Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7530, South Africa

^† Present address: Chemistry Department, Cape Peninsula University of Technology, P.O. BOX 1906, Bellville 7535, South Africa.

Molecules 2016, 21(11), 1498; https://doi.org/10.3390/molecules21111498 - 8 Nov 2016

Cited by 55 | Viewed by 7897

Abstract

The preparation of gold nanoparticles (AuNPs) involves a variety of chemical and physical methods. These methods use toxic and environmentally harmful chemicals. Consequently, the synthesis of AuNPs using green chemistry has been under investigation to develop eco-friendly nanoparticles. One approach to achieve this [...] Read more.

The preparation of gold nanoparticles (AuNPs) involves a variety of chemical and physical methods. These methods use toxic and environmentally harmful chemicals. Consequently, the synthesis of AuNPs using green chemistry has been under investigation to develop eco-friendly nanoparticles. One approach to achieve this is the use of plant-derived phytochemicals that are capable of reducing gold ions to produce AuNPs. The aim of this study was to implement a facile microtitre-plate method to screen a large number of aqueous plant extracts to determine the optimum concentration (OC) for the bio-synthesis of the AuNPs. Several AuNPs of different sizes and shapes were successfully synthesized and characterized from 17 South African plants. The characterization was done using Ultra Violet-Visible Spectroscopy, Dynamic Light Scattering, High Resolution Transmission Electron Microscopy and Energy-Dispersive X-ray Spectroscopy. We also studied the effects of temperature on the synthesis of the AuNPs and showed that changes in temperatures affect the size and dispersity of the generated AuNPs. We also evaluated the stability of the synthesized AuNPs and showed that some of them are stable in biological buffer solutions. Full article

(This article belongs to the Section Green Chemistry)

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11 pages, 1413 KiB

Open AccessArticle

Biocatalytic Synthesis of Novel Partial Esters of a Bioactive Dihydroxy 4-Methylcoumarin by Rhizopus oryzae Lipase (ROL)

by Vinod Kumar^1,2, Divya Mathur^3,4, Smriti Srivastava³, Shashwat Malhotra^3,5, Neha Rana³, Suraj K. Singh³, Brajendra K. Singh³, Ashok K. Prasad³, Anjani J. Varma⁶, Christophe Len⁷

, Ramesh C. Kuhad^2,6, Rajendra K. Saxena² and Virinder S. Parmar^3,6,8,*

¹ Centre of Innovative and Applied Bioprocessing (CIAB), SAS Nagar, Mohali 160 071, Punjab, India

² Department of Microbiology, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India

³ Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India

⁴ Department of Chemistry, Daulat Ram College, University of Delhi, Delhi 110 007, India

⁵ Department of Chemistry, Kirori Mal College, University of Delhi, Delhi 110 007, India

⁶ School of Chemical Sciences, Central University of Haryana, Mahendragarh, Haryana 123 029, India

⁷ Sorbonne Universités, Université de Technologie de Compiègne, EA4297 Transformations Chimiques de la Matière Renouvelable, F-60203 Compiègne CEDEX, France

⁸ Institute of Advanced Sciences, 410 Faunce Corner Mall Road, Dartmouth, MA 02747, USA

Molecules 2016, 21(11), 1499; https://doi.org/10.3390/molecules21111499 - 9 Nov 2016

Cited by 4 | Viewed by 6820

Abstract

Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the [...] Read more.

Highly regioselective acylation has been observed in 7,8-dihydroxy-4-methylcoumarin (DHMC) by the lipase from Rhizopus oryzae suspended in tetrahydrofuran (THF) at 45 °C using six different acid anhydrides as acylating agents. The acylation occurred regioselectively at one of the two hydroxy groups of the coumarin moiety resulting in the formation of 8-acyloxy-7-hydroxy-4-methylcoumarins, which are important bioactive molecules for studying biotansformations in animals, and are otherwise very difficult to obtain by only chemical steps. Six monoacylated, monohydroxy 4-methylcoumarins have been biocatalytically synthesised and identified on the basis of their spectral data and X-ray crystal analysis. Full article

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

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16 pages, 3547 KiB

Open AccessArticle

Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study

by Armaghan Shafaei¹, Md Shamsuddin Sultan Khan², Abdalrahim F. A. Aisha¹, Amin Malik Shah Abdul Majid², Mohammad Razak Hamdan³, Mohd Nizam Mordi³ and Zhari Ismail^1,*

¹ Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia

² EMAN Testing & Research Laboratory, Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia

³ Centre for Drug Research, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia

Molecules 2016, 21(11), 1500; https://doi.org/10.3390/molecules21111500 - 9 Nov 2016

Cited by 27 | Viewed by 8593

Abstract

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action [...] Read more.

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3′-hydroxy-5,6,7,4′-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure–activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT’s LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC₅₀ value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC₅₀ 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE. Full article

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

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18 pages, 4146 KiB

Open AccessArticle

Resveratrol and Coumarin: Novel Agricultural Antibacterial Agent against Ralstonia solanacearum In Vitro and In Vivo

by Juanni Chen, Yanmei Yu, Shili Li and Wei Ding^*

Laboratory of Natural Product Pesticide, College of Plant Protection, Southwest University, Chongqing 400715, China

Molecules 2016, 21(11), 1501; https://doi.org/10.3390/molecules21111501 - 9 Nov 2016

Cited by 53 | Viewed by 9628

Abstract

Bacterial wilt is a destructive disease caused by the phytopathogen Ralstonia solanacearum (R. solanacearum), which is widely found in various tobacco-growing areas all over the world. Botanical bactericidal substances have gradually emerged as a hot topic in modern pesticide research. In [...] Read more.

Bacterial wilt is a destructive disease caused by the phytopathogen Ralstonia solanacearum (R. solanacearum), which is widely found in various tobacco-growing areas all over the world. Botanical bactericidal substances have gradually emerged as a hot topic in modern pesticide research. In this study, the antibacterial activities of two phytochemicals (resveratrol and coumarin) against R. solanacearum and their in vivo and in vitro efficacy for controlling tobacco bacterial wilt were evaluated. We rule out significant biological effects of both phytochemicals using transmission electron microscope (TEM) and fluorescence microscope, which suppressed the growth of R. solanacearum. Furthermore, we demonstrated that the toxicity mechanisms mainly involved damaging bacterial cell membrane and preventing swarming motility and biofilm formation. A further pot experiment demonstrated that coumarin and resveratrol significantly inhibited early adhesion and colonization of R. solanacearum in tobacco plants and the corresponding control efficacies were 68% and 85% after incubation for 13 days, respectively. The findings of this study suggest that both resveratrol and coumarin have potential as non-toxic antimicrobial strategies for controlling tobacco bacterial wilt disease. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 3880 KiB

Open AccessArticle

Chemistry and Photochemistry of Anthocyanins and Related Compounds: A Thermodynamic and Kinetic Approach

by Nuno Basílio^*

and Fernando Pina^*

LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal

Molecules 2016, 21(11), 1502; https://doi.org/10.3390/molecules21111502 - 10 Nov 2016

Cited by 65 | Viewed by 8048

Abstract

Anthocyanins are identified by the respective flavylium cation, which is only one species of a multistate of different molecules reversibly interconverted by external inputs such as pH, light and temperature. The flavylium cation (acidic form) is involved in an apparent acid-base reaction, where [...] Read more.

Anthocyanins are identified by the respective flavylium cation, which is only one species of a multistate of different molecules reversibly interconverted by external inputs such as pH, light and temperature. The flavylium cation (acidic form) is involved in an apparent acid-base reaction, where the basic species is the sum of quinoidal base, hemiketal and cis- and trans-chalcones, their relative fraction depending on the substitution pattern of the flavylium cation. The full comprehension of this complex system requires a thermodynamic and kinetic approach. The first consists in drawing an energy level diagram where the relative positions of the different species are represented as a function of pH. On the other hand, the kinetic approach allows measuring the rates of the reactions that interconnect reversibly the multistate species. The kinetics is greatly dependent on the existence or not of a high cis-trans isomerization barrier. In this work, the procedure to obtain the energy level diagram and the rates of inter-conversion in the multistate in both cases (low or high isomerization barrier) are described. Practical examples of this approach are presented to illustrate the theory, and recently reported applications based on host–guest complexes are reviewed. Full article

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

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15 pages, 916 KiB

Open AccessArticle

Double Intramolecular Transacetalization of Polyhydroxy Acetals: Synthesis of Conformationally-Restricted 1,3-Dioxanes with Axially-Oriented Phenyl Moiety

by Samuel Asare-Nkansah¹ and Bernhard Wünsch^1,2,*

¹ Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Corrensstraße 48, D-48149 Münster, Germany

² Cells-in-Motion Cluster of Excellence (EXC 1003–CiM), Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany

Molecules 2016, 21(11), 1503; https://doi.org/10.3390/molecules21111503 - 9 Nov 2016

Cited by 7 | Viewed by 6780

Abstract

The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15), benzaldehyde acetal 12a and acetophenone ketal 12b bearing a protected 1,3,5-trihydroxypentyl side chain in the o [...] Read more.

The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15), benzaldehyde acetal 12a and acetophenone ketal 12b bearing a protected 1,3,5-trihydroxypentyl side chain in the o-position were prepared. The first acid-catalyzed intramolecular transacetalization gave a mixture of diastereomeric 2-benzofurans 18 (ratio of diastereomers 2:2:1:1). After OH group deprotection, the second intramolecular transacetalization afforded tricyclic alcohol 14a (2-(1,5-epoxy-1,3,4,5-tetrahydro-2-benzoxepin-3-yl]ethan-1-ol). Analogous cyclizations led to the corresponding silyl ether 22a (19%) and azide 23a (13%). Whereas tricyclic alcohol 14a was obtained as a 1:1 mixture of diastereomers, the silyl ether 22a and the azide 23a afforded only one diastereomer. This observation indicates a faster cyclization of the minor diastereomers providing the thermodynamically-favored compounds with equatorially-oriented substituents in the 3-position of the tricyclic 1,5-epoxy-2-benzoxepine system. In general, acetophenone-derived ketalic compounds (b-series) required very mild reaction conditions and gave lower yields than the corresponding acetalic compounds (a-series). Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 6045 KiB

Open AccessArticle

Unraveling the Roots of Selectivity of Peptide Affinity Reagents for Structurally Similar Ribosomal Inactivating Protein Derivatives

by Deborah A. Sarkes^*, Margaret M. Hurley and Dimitra N. Stratis-Cullum

Biotechnology Branch, Sensors and Electron Devices Directorate, US Army Research Laboratory, Adelphi, MD 20783, USA

Molecules 2016, 21(11), 1504; https://doi.org/10.3390/molecules21111504 - 9 Nov 2016

Cited by 7 | Viewed by 5772

Abstract

Peptide capture agents have become increasingly useful tools for a variety of sensing applications due to their ease of discovery, stability, and robustness. Despite the ability to rapidly discover candidates through biopanning bacterial display libraries and easily mature them to Protein Catalyzed Capture [...] Read more.

Peptide capture agents have become increasingly useful tools for a variety of sensing applications due to their ease of discovery, stability, and robustness. Despite the ability to rapidly discover candidates through biopanning bacterial display libraries and easily mature them to Protein Catalyzed Capture (PCC) agents with even higher affinity and selectivity, an ongoing challenge and critical selection criteria is that the peptide candidates and final reagent be selective enough to replace antibodies, the gold-standard across immunoassay platforms. Here, we have discovered peptide affinity reagents against abrax, a derivative of abrin with reduced toxicity. Using on-cell Fluorescence Activated Cell Sorting (FACS) assays, we show that the peptides are highly selective for abrax over RiVax, a similar derivative of ricin originally designed as a vaccine, with significant structural homology to abrax. We rank the newly discovered peptides for strongest affinity and analyze three observed consensus sequences with varying affinity and specificity. The strongest (Tier 1) consensus was FWDTWF, which is highly aromatic and hydrophobic. To better understand the observed selectivity, we use the XPairIt peptide–protein docking protocol to analyze binding location predictions of the individual Tier 1 peptides and consensus on abrax and RiVax. The binding location profiles on the two proteins are quite distinct, which we determine is due to differences in pocket size, pocket environment (including hydrophobicity and electronegativity), and steric hindrance. This study provides a model system to show that peptide capture candidates can be quite selective for a structurally similar protein system, even without further maturation, and offers an in silico method of analysis for understanding binding and down-selecting candidates. Full article

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16 pages, 4016 KiB

Open AccessArticle

cDNA Isolation and Functional Characterization of UDP-d-glucuronic Acid 4-Epimerase Family from Ornithogalum caudatum

by Sen Yin^†, Yu-Jia Sun^†, Ming Liu, Li-Na Li and Jian-Qiang Kong^*

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1505; https://doi.org/10.3390/molecules21111505 - 9 Nov 2016

Cited by 9 | Viewed by 5743

Abstract

d-Galacturonic acid (GalA) is an important component of GalA-containing polysaccharides in Ornithogalum caudatum. The incorporation of GalA into these polysaccharides from UDP-d-galacturonic acid (UDP-GalA) was reasonably known. However, the cDNAs involved in the biosynthesis of UDP-GalA were still unknown. [...] Read more.

d-Galacturonic acid (GalA) is an important component of GalA-containing polysaccharides in Ornithogalum caudatum. The incorporation of GalA into these polysaccharides from UDP-d-galacturonic acid (UDP-GalA) was reasonably known. However, the cDNAs involved in the biosynthesis of UDP-GalA were still unknown. In the present investigation, one candidate UDP-d-glucuronic acid 4-epimerase (UGlcAE) family with three members was isolated from O. caudatum based on RNA-Seq data. Bioinformatics analyses indicated all of the three isoforms, designated as OcUGlcAE1~3, were members of short-chain dehydrogenases/reductases (SDRs) and shared two conserved motifs. The three full-length cDNAs were then transformed to Pichia pastoris GS115 for heterologous expression. Data revealed both the supernatant and microsomal fractions from the recombinant P. pastoris expressing OcUGlcAE3 can interconvert UDP-GalA and UDP-d-glucuronic acid (UDP-GlcA), while the other two OcUGlcAEs had no activity on UDP-GlcA and UDP-GalA. Furthermore, expression analyses of the three epimerases in varied tissues of O. caudatum were performed by real-time quantitative PCR (RT-qPCR). Results indicated OcUGlcAE3, together with the other two OcUGlcAE-like genes, was root-specific, displaying highest expression in roots. OcUGlcAE3 was UDP-d-glucuronic acid 4-epimerase and thus deemed to be involved in the biosynthesis of root polysaccharides. Moreover, OcUGlcAE3 was proposed to be environmentally induced. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 833 KiB

Open AccessArticle

Anti-Complementary Components of Helicteres angustifolia

by Xiang Yin¹

, Yan Lu², Zhi-Hong Cheng² and Dao-Feng Chen^1,2,*

¹ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

² Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China

Molecules 2016, 21(11), 1506; https://doi.org/10.3390/molecules21111506 - 10 Nov 2016

Cited by 16 | Viewed by 5099

Abstract

A first phenalenon derivative with an acetyl side chain at C-8, 8-acetyl-9-hydroxy-3-methoxy-7-methyl-1-phenalenon (compound 1), and a pair of new sesquilignan epimers at C-7″ of hedyotol C and hedyotol D analogs, hedyotol C 7″-O-β-d-glucopyranoside (compound 2) and hedyotol [...] Read more.

A first phenalenon derivative with an acetyl side chain at C-8, 8-acetyl-9-hydroxy-3-methoxy-7-methyl-1-phenalenon (compound 1), and a pair of new sesquilignan epimers at C-7″ of hedyotol C and hedyotol D analogs, hedyotol C 7″-O-β-d-glucopyranoside (compound 2) and hedyotol D 7″-O-β-d-glucopyranoside (compound 3) were isolated from the aerial parts of Helicteres angustifolia together with nine known compounds (4–12). Their structures were elucidated on the basis of spectroscopic methods, including mass spectroscopy, and 1D and 2D nuclear magnetic resonance. Eleven isolates exhibited anti-complementary activity. In particular, compounds 4 and 5 exhibited potent anti-complementary activities against the classical and alternative pathways with CH₅₀ values of 0.040 ± 0.009 and 0.009 ± 0.002 mM, and AP₅₀ values of 0.105 ± 0.015 and 0.021 ± 0.003 mM, respectively. The targets of compounds 4 and 5 in the complement activation cascade were also identified. In conclusion, the anti-complementary components of H. angustifolia possessed chemical diversity and consisted mostly of flavonoids and lignans in this study. Full article

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16 pages, 11044 KiB

Open AccessArticle

TTF1, in the Form of Nanoparticles, Inhibits Angiogenesis, Cell Migration and Cell Invasion In Vitro and In Vivo in Human Hepatoma through STAT3 Regulation

by Bin Xiao^1,†, Dongjing Lin^2,†, Xuan Zhang¹, Meilan Zhang¹ and Xuewu Zhang^1,*

¹ College of Medicine, Yanbian University, Yanji 133000, China

² Basic Medical College, Jilin Medical University, Jilin 132013, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1507; https://doi.org/10.3390/molecules21111507 - 10 Nov 2016

Cited by 16 | Viewed by 7579

Abstract

TTF1-NP (5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showed its anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 [...] Read more.

TTF1-NP (5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showed its anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment. Full article

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15 pages, 2080 KiB

Open AccessArticle

Bee Venom Inhibits Porphyromonas gingivalis Lipopolysaccharides-Induced Pro-Inflammatory Cytokines through Suppression of NF-κB and AP-1 Signaling Pathways

by Woon-Hae Kim¹

, Hyun-Jin An¹, Jung-Yeon Kim¹, Mi-Gyeong Gwon¹, Hyemin Gu¹, Jae-Bok Park¹, Woo Jung Sung¹, Yong-Chul Kwon¹, Kyung-Duck Park²

, Sang Mi Han³ and Kwan-Kyu Park^1,*

¹ Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea

² Department of Dermatology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea

³ Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, 300, Nongsaengmyeong-ro, Wansan-gu, Jeonju-si 54875, Korea

Molecules 2016, 21(11), 1508; https://doi.org/10.3390/molecules21111508 - 10 Nov 2016

Cited by 23 | Viewed by 7046

Abstract

Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis (P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine [...] Read more.

Periodontitis is a chronic inflammatory disease that leads to destruction of tooth supporting tissues. Porphyromonas gingivalis (P. gingivalis), especially its lipopolysaccharides (LPS), is one of major pathogens that cause periodontitis. Bee venom (BV) has been widely used as a traditional medicine for various diseases. Previous studies have demonstrated the anti-inflammatory, anti-bacterial effects of BV. However, a direct role and cellular mechanism of BV on periodontitis-like human keratinocytes have not been explored. Therefore, we investigated the anti-inflammatory mechanism of BV against P. gingivalis LPS (PgLPS)-induced HaCaT human keratinocyte cell line. The anti-inflammatory effect of BV was demonstrated by various molecular biological methods. The results showed that PgLPS increased the expression of Toll-like receptor (TLR)-4 and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and interferon (IFN)-γ. In addition, PgLPS induced activation of the signaling pathways of inflammatory cytokines-related transcription factors, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). BV effectively inhibited those pro-inflammatory cytokines through suppression of NF-κB and AP-1 signaling pathways. These results suggest that administration of BV attenuates PgLPS-induced inflammatory responses. Furthermore, BV may be a useful treatment to anti-inflammatory therapy for periodontitis. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 885 KiB

Open AccessArticle

Enantioselective Analytical- and Preparative-Scale Separation of Hexabromocyclododecane Stereoisomers Using Packed Column Supercritical Fluid Chromatography

by Nicole Riddell^1,2,*, Lauren Gayle Mullin^2,3, Bert Van Bavel^2,4, Ingrid Ericson Jogsten²

, Alan McAlees¹, Allison Brazeau¹, Scott Synnott¹, Alan Lough⁵, Robert McCrindle^1,6 and Brock Chittim¹

¹ Wellington Laboratories Inc., 345 Southgate Drive, Guelph, ON N1G 3M5, Canada

² Man-Technology-Environment (MTM) Research Center, Örebro University, 70182 Örebro, Sweden

³ Waters Corporation, 34 Maple Street, Milford, MA 01757, USA

⁴ Norwegian Institute for Water Research, NO-349 Oslo, Norway

⁵ Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada

⁶ Chemistry Department, University of Guelph, Guelph, ON N1G 2W1, Canada

Molecules 2016, 21(11), 1509; https://doi.org/10.3390/molecules21111509 - 10 Nov 2016

Cited by 7 | Viewed by 6516

Abstract

Hexabromocyclododecane (HBCDD) is an additive brominated flame retardant which has been listed in Annex A of the Stockholm Convention for elimination of production and use. It has been reported to persist in the environment and has the potential for enantiomer-specific degradation, accumulation, or [...] Read more.

Hexabromocyclododecane (HBCDD) is an additive brominated flame retardant which has been listed in Annex A of the Stockholm Convention for elimination of production and use. It has been reported to persist in the environment and has the potential for enantiomer-specific degradation, accumulation, or both, making enantioselective analyses increasingly important. The six main stereoisomers of technical HBCDD (i.e., the (+) and (−) enantiomers of α-, β-, and γ-HBCDD) were separated and isolated for the first time using enantioselective packed column supercritical fluid chromatography (pSFC) separation methods on a preparative scale. Characterization was completed using published chiral liquid chromatography (LC) methods and elution profiles, as well as X-ray crystallography, and the isolated fractions were definitively identified. Additionally, the resolution of the enantiomers, along with two minor components of the technical product (δ- and ε-HBCDD), was investigated on an analytical scale using both LC and pSFC separation techniques, and changes in elution order were highlighted. Baseline separation of all HBCDD enantiomers was achieved by pSFC on an analytical scale using a cellulose-based column. The described method emphasizes the potential associated with pSFC as a green method of isolating and analyzing environmental contaminants of concern. Full article

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

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25 pages, 3412 KiB

Open AccessReview

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

by Neill Kim^1,†, Olga Estrada^1,†, Benjamin Chavez¹, Charles Stewart²

and John C. D’Auria^1,*

¹ Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA

² Office of Biotechnology, Iowa State University, Ames, IA 50011-1079, USA

^† These authors contributed equally to this article.

Molecules 2016, 21(11), 1510; https://doi.org/10.3390/molecules21111510 - 11 Nov 2016

Cited by 56 | Viewed by 16502

Abstract

The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may [...] Read more.

The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring to their core ring structures. Throughout much of human history, humans have cultivated tropane- and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis. In addition, modern approaches to producing some pharmaceutically important tropanes via metabolic engineering endeavors are discussed. Full article

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

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13 pages, 2939 KiB

Open AccessArticle

Simultaneous Determination of Coumarin and Its Derivatives in Tobacco Products by Liquid Chromatography-Tandem Mass Spectrometry

by Zhiqin Ren^1,†, Bo Nie^2,†, Tong Liu¹, Fei Yuan¹, Feng Feng¹, Yuan Zhang¹, Weie Zhou¹, Xiuli Xu¹, Meiyi Yao¹ and Feng Zhang^1,*

¹ Institute of Food Safety (Tobacco Safety and Control Technology Center), Chinese Academy of Inspection & Quarantine, Beijing 100176, China

² Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1511; https://doi.org/10.3390/molecules21111511 - 10 Nov 2016

Cited by 33 | Viewed by 7131

Abstract

In this paper an analytical method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the determination of coumarin and its derivatives in tobacco products was developed. The MS/MS fragmentation pathways of the eight coumarins were elucidated. The new [...] Read more.

In this paper an analytical method based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the determination of coumarin and its derivatives in tobacco products was developed. The MS/MS fragmentation pathways of the eight coumarins were elucidated. The new analytical method was defined based on two main axes, an extraction procedure with acetonitrile and analyte detection performed by HPLC-MS/MS in electron impact mode. The excellent selectivity and sensitivity achieved in multiple reaction monitoring (MRM) mode allowed satisfactory confirmation and quantitation for the coumarin flavor additives. Under the optimized gradient elution conditions, it took only 4.5 min to separate all eight coumarins. Good linearity for all the analytes were confirmed by the correlation coefficient r², ranging from 0.9987 to 0.9996. The limits of detection (LODs) and limits of quantitation (LOQs) of these compounds were in the range of 0.5–1.7 μg/kg and 1.7–5.2 μg/kg, respectively. The average recoveries at three spiked levels (LOQ, 1.5LOQ, 2LOQ) were all in the range of 69.6%–95.1% with RSDs (n = 6) lower than 5.3%. The method of HPLC-MS/MS developed in this study was initially applied to the research of coumarin flavor additives in tobacco products collected from the located market in Beijing from China and proved to be accurate, sensitive, convenient and practical. Full article

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32 pages, 1110 KiB

Open AccessReview

The Complexity of Targeting PI3K-Akt-mTOR Signalling in Human Acute Myeloid Leukaemia: The Importance of Leukemic Cell Heterogeneity, Neighbouring Mesenchymal Stem Cells and Immunocompetent Cells

by Annette K. Brenner¹, Tor Henrik Andersson Tvedt^1,2 and Øystein Bruserud^1,2,*

¹ Section for Haematology, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway

² Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway

Molecules 2016, 21(11), 1512; https://doi.org/10.3390/molecules21111512 - 11 Nov 2016

Cited by 43 | Viewed by 15563

Abstract

Therapeutic targeting of PI3K-Akt-mTOR is considered a possible strategy in human acute myeloid leukaemia (AML); the most important rationale being the proapoptotic and antiproliferative effects of direct PI3K/mTOR inhibition observed in experimental studies of human AML cells. However, AML is a heterogeneous disease [...] Read more.

Therapeutic targeting of PI3K-Akt-mTOR is considered a possible strategy in human acute myeloid leukaemia (AML); the most important rationale being the proapoptotic and antiproliferative effects of direct PI3K/mTOR inhibition observed in experimental studies of human AML cells. However, AML is a heterogeneous disease and these effects caused by direct pathway inhibition in the leukemic cells are observed only for a subset of patients. Furthermore, the final effect of PI3K-Akt-mTOR inhibition is modulated by indirect effects, i.e., treatment effects on AML-supporting non-leukemic bone marrow cells. In this article we focus on the effects of this treatment on mesenchymal stem cells (MSCs) and monocytes/macrophages; both these cell types are parts of the haematopoietic stem cell niches in the bone marrow. MSCs have unique membrane molecule and constitutive cytokine release profiles, and mediate their support through bidirectional crosstalk involving both cell-cell contact and the local cytokine network. It is not known how various forms of PI3K-Akt-mTOR targeting alter the molecular mechanisms of this crosstalk. The effect on monocytes/macrophages is also difficult to predict and depends on the targeted molecule. Thus, further development of PI3K-Akt-mTOR targeting into a clinical strategy requires detailed molecular studies in well-characterized experimental models combined with careful clinical studies, to identify patient subsets that are likely to respond to this treatment. Full article

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40 pages, 12236 KiB

Open AccessReview

Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity

by Pedro Laborda, Su-Yan Wang and Josef Voglmeir^*

Glycomics and Glycan Bioengineering Research Center, College of Food Science and Technology, Nanjing Agricultural University, 1 Weigang, Nanjing 210095, China

Molecules 2016, 21(11), 1513; https://doi.org/10.3390/molecules21111513 - 11 Nov 2016

Cited by 67 | Viewed by 22900

Abstract

Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release [...] Read more.

Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release of viruses from infected host cells. The treatment of influenza is mainly based on the administration of neuraminidase inhibitors. The neuraminidase inhibitors zanamivir, laninamivir, oseltamivir and peramivir have been commercialized and have been demonstrated to be potent influenza viral neuraminidase inhibitors against most influenza strains. In order to create more potent neuraminidase inhibitors and fight against the surge in resistance resulting from naturally-occurring mutations, these anti-influenza drugs have been used as templates for the development of new neuraminidase inhibitors through structure-activity relationship studies. Here, we review the synthetic routes to these commercial drugs, the modifications which have been performed on these structures and the effects of these modifications on their inhibitory activity. Full article

(This article belongs to the Collection Advances in Glycosciences)

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16 pages, 2920 KiB

Open AccessArticle

Kinetic Spectrophotometric Method for the 1,4-Diionic Organophosphorus Formation in the Presence of Meldrum′s Acid: Stopped-Flow Approach

by Fatemeh Ghodsi, Sayyed Mostafa Habibi-Khorassani and Mehdi Shahraki^*

Department of Chemistry, University of Sistan and Baluchestan, P.O. Box 98135-674, Zahedan 9816744599, Iran

Molecules 2016, 21(11), 1514; https://doi.org/10.3390/molecules21111514 - 11 Nov 2016

Cited by 15 | Viewed by 5476

Abstract

The kinetics of the reaction between triphenylphosphine (TPP) and dimethyl acetylenedicarboxylate (DMAD) in the presence of Meldrum’s acid (MA) for the generation of the 1,4-diionic organophosphorus compound has been investigated using the stopped-flow and UV-VIS spectrophotometry techniques. The first step of the reaction [...] Read more.

The kinetics of the reaction between triphenylphosphine (TPP) and dimethyl acetylenedicarboxylate (DMAD) in the presence of Meldrum’s acid (MA) for the generation of the 1,4-diionic organophosphorus compound has been investigated using the stopped-flow and UV-VIS spectrophotometry techniques. The first step of the reaction between TPP and DMAD for the generation of (I₁) in ethanol was followed by the stopped-flow apparatus. This step was recognized as a fast step. The reaction between the intermediate (I₁) and MA showed first-order kinetics, and it was followed by the UV-VIS spectrophotometry technique. The activation parameters for the slow step of the proposed mechanism were determined using two linearized forms of the Eyring equation. From the temperature, concentration and solvent studies, the activation energy (Ea = 20.16 kJ·mol⁻¹) and the related activation parameters (ΔG^‡ = 71.17 ± 0.015 kJ·mol⁻¹, ΔS^‡ = −185.49 ± 0.026 J·mol⁻¹ and ΔH^‡ =17.72 ± 0.007 kJ·mol⁻¹) were calculated. The experimental data indicated that the reaction was zero-order in MA and second-order overall. The proposed mechanism was confirmed with the observed kinetic data obtained from the UV-VIS and stopped-flow techniques. Full article

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

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13 pages, 1777 KiB

Open AccessArticle

Inhibitory Interactions of Aspalathus linearis (Rooibos) Extracts and Compounds, Aspalathin and Z-2-(β-d-Glucopyranosyloxy)-3-phenylpropenoic Acid, on Cytochromes Metabolizing Hypoglycemic and Hypolipidemic Drugs

by Oelfah Patel^1,4, Christo Muller^1,*

, Elizabeth Joubert^2,3

, Johan Louw¹, Bernd Rosenkranz⁴ and Charles Awortwe^1,4

¹ Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa

² Post-Harvest and Wine Technology Division, Agricultural Research Council, Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa

³ Department of Food Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa

⁴ Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Stellenbosch, P.O. Box 241, Cape Town 8000, South Africa

Molecules 2016, 21(11), 1515; https://doi.org/10.3390/molecules21111515 - 12 Nov 2016

Cited by 35 | Viewed by 7921

Abstract

Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, [...] Read more.

Rooibos extract, due to its glucose and lipid lowering effects, has potential as a nutraceutical for improvement of metabolic dysfunction. Potential herb-drug interactions as a result of the use of natural products are of increasing concern. Cytochrome P450 enzymes, CYP2C8, CYP2C9, and CYP3A4, are important in the metabolism of hypoglycemic drugs, such as thiazolidinediones (TZDs) and sulfonylureas, and hypocholesterolemic drugs, such as atorvastatin. This study investigated the effects of rooibos extracts, prepared from “unfermented” and “fermented” rooibos plant material and two of the major bioactive compounds, Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid (PPAG) and aspalathin (ASP), on Vivid^® recombinant CYP450 enzymes. Unfermented (GRT) and fermented (FRE) rooibos extracts inhibited the activity of CYP2C8 (7.69 ± 8.85 µg/mL and 8.93 ± 8.88 µg/mL, respectively) and CYP3A4 (31.33 ± 4.69 µg/mL and 51.44 ± 4.31 µg/mL, respectively) based on their respective IC₅₀ concentrations. Both extracts dose- and time-dependently inhibited CYP2C8 activity, but only time-dependently inhibited CYP2C9. CYP3A4 showed concentration-dependent inhibition by ASP, GRT, and FRE at 25, 50, and 100 µg/mL concentrations. ASP, GRT, and FRE time-dependently inhibited CYP3A4 activity with GRT and FRE showing a more potent time-dependent inhibition, comparable to erythromycin. These findings suggest that herb-drug interactions may occur when nutraceuticals containing rooibos extracts are co-administered with hypoglycemic drugs such as TZDs, sulfonylureas, and dyslipidemic drug, atorvastatin. Full article

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16 pages, 1100 KiB

Open AccessReview

Ligand Fishing: A Remarkable Strategy for Discovering Bioactive Compounds from Complex Mixture of Natural Products

by Rongjie Zhuo^1,*,†, Hao Liu^2,†, Ningning Liu³ and Yi Wang^2,*

¹ Faculty of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China

² College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

³ TCM Research Center, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1516; https://doi.org/10.3390/molecules21111516 - 11 Nov 2016

Cited by 95 | Viewed by 12509

Abstract

Identification of active compounds from natural products is a critical and challenging task in drug discovery pipelines. Besides commonly used bio-guided screening approaches, affinity selection strategy coupled with liquid chromatography or mass spectrometry, known as ligand fishing, has been gaining increasing interest from [...] Read more.

Identification of active compounds from natural products is a critical and challenging task in drug discovery pipelines. Besides commonly used bio-guided screening approaches, affinity selection strategy coupled with liquid chromatography or mass spectrometry, known as ligand fishing, has been gaining increasing interest from researchers. In this review, we summarized this emerging strategy and categorized those methods as off-line or on-line mode according to their features. The separation principles of ligand fishing were introduced based on distinct analytical techniques, including biochromatography, capillary electrophoresis, ultrafiltration, equilibrium dialysis, microdialysis, and magnetic beads. The applications of ligand fishing approaches in the discovery of lead compounds were reviewed. Most of ligand fishing methods display specificity, high efficiency, and require less sample pretreatment, which makes them especially suitable for screening active compounds from complex mixtures of natural products. We also summarized the applications of ligand fishing in the modernization of Traditional Chinese Medicine (TCM), and propose some perspectives of this remarkable technique. Full article

(This article belongs to the Special Issue New Methodologies in Natural Product Analytics and Structure Elucidation)

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13 pages, 4602 KiB

Open AccessArticle

Selenium Nanoparticles Attenuate Oxidative Stress and Testicular Damage in Streptozotocin-Induced Diabetic Rats

by Mohamed A. Dkhil^1,2, Rafat Zrieq³

, Saleh Al-Quraishy¹ and Ahmed E. Abdel Moneim^2,*

¹ Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

² Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt

³ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hail, Hail 2440, Saudi Arabia

Molecules 2016, 21(11), 1517; https://doi.org/10.3390/molecules21111517 - 19 Nov 2016

Cited by 100 | Viewed by 9706

Abstract

We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the [...] Read more.

We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the rat testes were assessed. Biochemical analysis revealed that SeNPs are able to ameliorate the reduction in the serum testosterone caused by STZ-induced diabetes. Furthermore, SeNPs could significantly decrease testicular tissue oxidative stress markers, namely lipid peroxidation and nitric oxide. In contrast, treatment of the STZ-diabetic rats with SeNPs increased the glutathione content and antioxidant enzyme activities in testicular tissues. Moreover, microscopic analysis proved that SeNPs are able to prevent histological damage in the testes of STZ-diabetic rats. Molecular analysis revealed that the mRNA level of Bcl-2 (B-cell lymphoma 2) is significantly upregulated. On the contrary, the mRNA level of Bax (Bcl-2 Associated X Protein) was significantly downregulated. Furthermore, treatment of STZ-diabetic rats with SeNPs led to an elevation in the expression of PCNA (Proliferating Cell Nuclear Antigen Gene). Interestingly, the insulin treatment also exhibited a significant improvement in the testicular function in STZ-diabetic rats. Collectively, our results demonstrated the possible effects of SeNPs in attenuating diabetes-induced oxidative damage, in particular in testicular tissue. Full article

(This article belongs to the Special Issue Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospectives)

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12 pages, 1768 KiB

Open AccessArticle

Development of Amylose- and β-Cyclodextrin-Based Chiral Fluorescent Sensors Bearing Terthienyl Pendants

by Tomoyuki Ikai^*, Changsik Yun

, Yutaka Kojima, Daisuke Suzuki, Katsuhiro Maeda and Shigeyoshi Kanoh

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan

Molecules 2016, 21(11), 1518; https://doi.org/10.3390/molecules21111518 - 11 Nov 2016

Cited by 11 | Viewed by 6480

Abstract

Phenylcarbamate derivatives of amylose and β-cyclodextrin show excellent chiral recognition when used as chiral stationary phases (CSPs) for high-performance liquid chromatography. To open up new possibilities of carbohydrate-based materials, we developed chiral fluorescent sensors based on amylose and β-cyclodextrin (Am-1b and CyD- [...] Read more.

Phenylcarbamate derivatives of amylose and β-cyclodextrin show excellent chiral recognition when used as chiral stationary phases (CSPs) for high-performance liquid chromatography. To open up new possibilities of carbohydrate-based materials, we developed chiral fluorescent sensors based on amylose and β-cyclodextrin (Am-1b and CyD-1b, respectively) by attaching fluorescent π-conjugated units on their side chains. Their recognition abilities toward chiral analytes containing a nitrophenyl unit were evaluated by measuring the enantioselective fluorescence quenching behavior. Both sensors showed the same degree of enantioselective fluorescence response for various aromatic nitro compounds. However, in some cases, their enantioselectivities were different depending on the analytes. The difference in the chiral recognition abilities between Am-1b and CyD-1b seems to be based on the structural difference of their inherent backbones, that is, the one-handed helical structure and cyclic structure, respectively. The study on the resolution ability of the Am-1b-based CSP revealed that the terthienyl-based pendant of Am-1b provides not only a fluorescent functionality but also a different chiral recognition site from that of amylose tris(phenylcarbamate). Full article

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

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19 pages, 11367 KiB

Open AccessArticle

Characteristics of the Protoporphyrin IX Binding Sites on Human Serum Albumin Using Molecular Docking

by Leszek Sułkowski^1,*

, Bartosz Pawełczak², Mariola Chudzik² and Małgorzata Maciążek-Jurczyk²

¹ Department of General and Vascular Surgery, Regional Specialist Hospital, Bialska 104/118, 42-218 Częstochowa, Poland

² Department of Physical Pharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland

Molecules 2016, 21(11), 1519; https://doi.org/10.3390/molecules21111519 - 17 Nov 2016

Cited by 24 | Viewed by 7736

Abstract

Human serum albumin (HSA) is the main plasma protein responsible for a distribution of drugs in the human circulatory system. The binding to HSA is one of the factors that determines both the pharmacological actions and the side effects of drugs. The derivative [...] Read more.

Human serum albumin (HSA) is the main plasma protein responsible for a distribution of drugs in the human circulatory system. The binding to HSA is one of the factors that determines both the pharmacological actions and the side effects of drugs. The derivative of heme, protoporphyrin IX (PpIX), is a hydrophobic photosensitizer widely used in photodynamic diagnosis and therapy of various malignant disorders. Using absorption and fluorescence spectroscopy, it has been demonstrated that PpIX forms complexes with HSA. Its binding sites in the tertiary structure of HSA were found in the subdomains IB and IIA. PpIX binds to HSA in one class of binding sites with the association constant of 1.68 × 10⁵ M⁻¹ and 2.30 × 10⁵ M⁻¹ for an excitation at wavelength λ_ex = 280 nm and 295 nm, respectively. The binding interactions between HSA and PpIX have been studied by means of molecular docking simulation using the CLC Drug Discovery Workbench (CLC DDWB) computer program. PpIX creates a strong ‘sandwich-type’ complex between its highly conjugated porphine system and aromatic side chains of tryptophan and tyrosine. In summary, fluorescent studies on binding interactions between HSA and PpIX have been confirmed by the results of computer simulation. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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15 pages, 1769 KiB

Open AccessArticle

Transdermal Permeation and Anti-Inflammation Activities of Novel Sinomenine Derivatives

by Zi-Jian Zhao^1,*, Chang Zhao², Jing Xiao³ and Jian-Cheng Wang³

¹ College of Chemistry and Materials Engineering, Huaihua University, Huaihua 418000, Hunan, China

² Huaihua No. 3 High School, Huaihua 418000, Hunan, China

³ College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, Hunan, China

Molecules 2016, 21(11), 1520; https://doi.org/10.3390/molecules21111520 - 17 Nov 2016

Cited by 15 | Viewed by 5162

Abstract

Sinomenine is extracted from Sinomenii caulis (a traditional Chinese medicine), and it is used as the active ingredient in rheumatic arthritis treatments. It has been used in clinical applications for decades. However, there are some disadvantages, including low activity in transdermal permeation and [...] Read more.

Sinomenine is extracted from Sinomenii caulis (a traditional Chinese medicine), and it is used as the active ingredient in rheumatic arthritis treatments. It has been used in clinical applications for decades. However, there are some disadvantages, including low activity in transdermal permeation and a high dosage being clinically required. To overcome these defects, sinomenine was used as a primer, and structural modification was performed. In our study, eight new compounds were screened out by transdermal permeation in vitro and anti-inflammatory response in vitro and in vivo. Compound 1a exhibited the most potent transdermal permeation and anti-inflammatory activity. Based on these results, further development of this compound may be warranted. Full article

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

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7 pages, 406 KiB

Open AccessShort Note

Anti-Inflammatory Chemical Profiling of the Australian Rainforest Tree Alphitonia petriei (Rhamnaceae)

by Ritesh Raju^1,3, Dhanushka Gunawardena¹, Most Afia Ahktar¹, Mitchell Low⁴

, Paul Reddell² and Gerald Münch^1,3,*

¹ School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia

² Ecobiotics Limited, 7 Penda Street, Yungaburra, QLD 4884, Australia

³ Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia

⁴ National Institute of Complementary Medicine (NICM), Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia

Molecules 2016, 21(11), 1521; https://doi.org/10.3390/molecules21111521 - 11 Nov 2016

Cited by 27 | Viewed by 7454

Abstract

Chronic inflammation is an important pathological condition in many human diseases, and due to the side effects of the currently used non-steroidal anti-inflammatory drugs, discovery of novel anti-inflammatory drugs is of general interest. Anti-inflammatory activity guided compound isolation from the plant Alphitonia petriei [...] Read more.

Chronic inflammation is an important pathological condition in many human diseases, and due to the side effects of the currently used non-steroidal anti-inflammatory drugs, discovery of novel anti-inflammatory drugs is of general interest. Anti-inflammatory activity guided compound isolation from the plant Alphitonia petriei led to the isolation of the known plant sterols emmolic acid (1), alphitolic acid (2), trans- and cis-coumaroyl esters of alphitolic acid (3 and 4) and betulinic acid (5). A detailed spectroscopic analysis led to the structure elucidation of the alphitolic acid derivatives (1–5), and the semi-synthetic emmolic acid acetate (6). When tested in LPS (Lipopolysaccharides) + IFN-γ (Interferon gamma) activated RAW 264.7 macrophages, all compounds except (1) exhibited potent anti-inflammatory activity (IC₅₀ values as low as 1.7 μM) in terms of downregulation of NO and TNF-α production, but also demonstrated some considerable cytotoxicity. Full article

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

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17 pages, 2929 KiB

Open AccessArticle

CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice

by AbuZar Ansari¹, Shambhunath Bose², Mukesh Kumar Yadav³, Jing-Hua Wang¹

, Yun-Kyung Song⁴, Seong-Gyu Ko⁵ and Hojun Kim^1,*

¹ Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, 814-Siksa-dong, Goyang, Gyeonggi-do 10326, South Korea

² NosQuest, 463-400 USPACE 1A-1103, Daewang Pangyoro 660, Bundanggu, Seongnamsi, Gyeonggi-do 13494, South Korea

³ Department of Otorhinolaryngology Head and Neck Surgery & Institute for Medical Device Clinical Trials, College of Medicine, Korea University, 148 Gurodong-ro, Guro-gu, Seoul 08308, South Korea

⁴ Department of Korean Rehabilitation Medicine, College of Korean Medicine, Gachon University, Incheon 22318, South Korea

⁵ Department of Preventive Medicine, College of Korean Medicine, Kyunghee University, Seoul 02453, South Korea

Molecules 2016, 21(11), 1522; https://doi.org/10.3390/molecules21111522 - 11 Nov 2016

Cited by 29 | Viewed by 10790

Abstract

The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of [...] Read more.

The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD) or high-fat diet (HFD) in absence or presence of CST or orlistat (ORL) for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y), and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript) in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4) and increased the mRNA level of obesity-suppressing adipokine (adiponectin) in visceral adipose tissue (VAT). Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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10 pages, 1393 KiB

Open AccessArticle

Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis

by Siti Fadziyah Mohamad Asri^1,2,*

, Elvy Suhana Mohd Ramli¹, Ima Nirwana Soelaiman³, Muhamad Alfakry Mat Noh⁴, Abdul Hamid Abdul Rashid⁵ and Farihah Suhaimi^1,*

¹ Department of Anatomy, Faculty of Medicines, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia

² Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

³ Department of Pharmacology, Faculty of Medicines, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia

⁴ Department of Anatomy, Faculty of Medicine, Universiti Malaya Medical Centre (UMMC), 59100 Lembah Pantai, Kuala Lumpur, Malaysia

⁵ Anatomy Unit, Basic Medical Science Cluster, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia

Molecules 2016, 21(11), 1523; https://doi.org/10.3390/molecules21111523 - 15 Nov 2016

Cited by 12 | Viewed by 5750

Abstract

Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase [...] Read more.

Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration (p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment. Full article

(This article belongs to the Collection Herbal Medicine Research)

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2 pages, 140 KiB

Open AccessEditorial

Special Issue “Molecular Engineering for Electrochemical Power Sources”

by Sergei Manzhos

Department of Mechanical Engineering, National University of Singapore, Block EA #07-08, 9 Engineering Drive 1, Singapore 1175761, Singapore

Molecules 2016, 21(11), 1524; https://doi.org/10.3390/molecules21111524 - 12 Nov 2016

Viewed by 3315

Abstract

Electrochemical energy conversion and storage technologies are expected to play an increasingly prominent role in the production and consumption of electricity in the coming decades.[...] Full article

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

40 pages, 7382 KiB

Open AccessReview

Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review

by Md Toufiqur Rahman

, Veera V. N. Phani Babu Tiruveedhula and James M. Cook^*

Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer Street, Milwaukee, WI 53201, USA

Molecules 2016, 21(11), 1525; https://doi.org/10.3390/molecules21111525 - 14 Nov 2016

Cited by 49 | Viewed by 12376

Abstract

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of [...] Read more.

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of monomeric indole alkaloids. Herein is reviewed the enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the Alstonia genus of the Apocynaceae family. The monomeric units belong to the sarpagine, ajmaline, macroline, vobasine, and pleiocarpamine series. An up-to-date discussion of their isolation, characterization, biological activity as well as approaches to their partial and total synthesis by means of both synthetic and biosynthetic strategies are presented. Full article

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

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12 pages, 1281 KiB

Open AccessArticle

The Use of Grape Seed Byproducts Rich in Flavonoids to Improve the Antioxidant Potential of Red Wines

by María José Jara-Palacios¹, Dolores Hernanz², María Luisa Escudero-Gilete¹

and Francisco J. Heredia^1,*

¹ Food Colour & Quality Laboratory, Department of Nutrition & Food Science, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain

² Department of Analytical Chemistry, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain

Molecules 2016, 21(11), 1526; https://doi.org/10.3390/molecules21111526 - 12 Nov 2016

Cited by 38 | Viewed by 7843

Abstract

The influence of adding seeds from grape pomace during Syrah wine fermentation in a warm climate has been studied. Seeds of Pedro Ximenez variety were rich in phenolic compounds, mainly flavonoids such as catechin and procyanidins. Changes in total phenolic content (TPC), total [...] Read more.

The influence of adding seeds from grape pomace during Syrah wine fermentation in a warm climate has been studied. Seeds of Pedro Ximenez variety were rich in phenolic compounds, mainly flavonoids such as catechin and procyanidins. Changes in total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity of red wines were observed. These changes depended on the vinification stage and the amount of seeds (SW: 450 g or DW: 900 g seeds/150 kg grapes) applied. In general, antioxidant activity was greater when a simple dose (SW) was considered. Results indicate that seeds rich in flavonoids could be used as wine additives, which could improve the antioxidant potential of red wines in a warm climate. Full article

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

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3 pages, 154 KiB

Open AccessEditorial

Special Issue: “Organic Reactions in Green Solvents”

by Jonathan Sperry^1,* and Joaquín García-Álvarez^2,*

¹ Centre for Green Chemical Science, School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland 1000, New Zealand

² Laboratorio de Compuestos Organometálicos y Catálisis (Unidad Asociada al CSIC), Departamento de Química Orgánica e Inorgánica, (IUQOEM), Centro de Innovación en Química Avanzada (ORFEO-CINQA), Facultad de Química, Universidad de Oviedo, Oviedo E-33071, Spain

Molecules 2016, 21(11), 1527; https://doi.org/10.3390/molecules21111527 - 15 Nov 2016

Cited by 19 | Viewed by 5500

Abstract

To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called Green Solvents. In this sense, the choice of [...] Read more.

To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called Green Solvents. In this sense, the choice of a safe, non-toxic, biorenewable and cheap reaction media is a crucial goal in organic synthesis. Thus, this Special Issue on “Organic Reactions in Green Solvents” has been aimed to showcase a series of stimulating contributions from international experts within different sub-areas of organic synthesis in Green Solvents (ranging from metal- to organo-catalyzed organic reactions). Full article

(This article belongs to the Special Issue Organic Reaction in Green Solvents)

13 pages, 4295 KiB

Open AccessArticle

Eluent Tolerance and Enantioseparation Recovery of Chiral Packing Materials Based on Chitosan Bis(Phenylcarbamate)-(n-Octyl Urea)s for High Performance Liquid Chromatography

by Jing Wang¹, Shao-Hua Huang², Wei Chen¹ and Zheng-Wu Bai^1,*

¹ School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430073, China

² Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China

Molecules 2016, 21(11), 1528; https://doi.org/10.3390/molecules21111528 - 13 Nov 2016

Cited by 15 | Viewed by 5164

Abstract

The goal of the present work was to study the influence of the swelling of chitosan derivatives on the enantioseparation and the separation performance recovery of chiral stationary phases (CSPs) based on these derivatives. Therefore, six chitosan bis(phenylcarbamate)-(n-octyl urea)s were synthesized, [...] Read more.

The goal of the present work was to study the influence of the swelling of chitosan derivatives on the enantioseparation and the separation performance recovery of chiral stationary phases (CSPs) based on these derivatives. Therefore, six chitosan bis(phenylcarbamate)-(n-octyl urea)s were synthesized, which were coated on macroporous 3-aminopropyl silica gel affording new CSPs. Most of the CSPs demonstrated strong enantioseparation capability for the tested chiral compounds. The swelling capacity of the chitosan bis(phenylcarbamate)-(n-octyl urea)s in ethyl acetate, acetone and tetrahydrofuran (THF) was evaluated. Among the chitosan derivatives, the chitosan bis(3,5-dichlorophenylcarbamate)-(n-octyl urea) polymer showed the highest swelling capacity in ethyl acetate and THF. The polymer-based CSPs could be utilized with pure ethyl acetate and a normal phase containing 70% THF, but was damaged by pure THF. On the other hand, the separation performance of the damaged CSP could be recovered after it was allowed to stand for a period of time. The observations are important for the development and application of polysaccharide derivative-based CSPs. Full article

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15 pages, 6074 KiB

Open AccessFeature PaperReview

Recent Progress in the Molecular Recognition and Therapeutic Importance of Interleukin-1 Receptor-Associated Kinase 4

by Mahesh Chandra Patra

and Sangdun Choi^*

Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea

Molecules 2016, 21(11), 1529; https://doi.org/10.3390/molecules21111529 - 13 Nov 2016

Cited by 36 | Viewed by 12139

Abstract

Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the cell, which detect pathogen associated molecular patterns and initiate signal transduction, culminating in the transcription of pro-inflammatory cytokines and antiviral interferon. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key mediator in [...] Read more.

Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the cell, which detect pathogen associated molecular patterns and initiate signal transduction, culminating in the transcription of pro-inflammatory cytokines and antiviral interferon. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key mediator in TLR (except for TLR3) and interleukin-1 receptor signaling pathways. The loss of kinase function of IRAK4 is associated with increased susceptibility to various pathogens, while its over-activation causes autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and cancer. The therapeutic importance of this master kinase has been advocated by a number of recent preclinical studies, where potent inhibitors have been administered to improve various TLR-mediated pathologies. Increasing studies of X-ray crystallographic structures with bound inhibitors have improved our knowledge on the molecular recognition of ligands by IRAK4, which will be crucial for the development of new inhibitors with improved potencies. In this review, we briefly discuss the structural aspect of ligand recognition by IRAK4 and highlight its therapeutic importance in the context of TLR-associated unmet medical needs. Full article

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39 pages, 4559 KiB

Open AccessFeature PaperReview

The Chemistry and Pharmacology of Citrus Limonoids

by Roberta Gualdani¹, Maria Maddalena Cavalluzzi², Giovanni Lentini^2,*

and Solomon Habtemariam^3,*

¹ Department of Chemistry ”U. Shiff”, University of Florence, Via della Lastruccia 3, Florence 50019, Italy

² Department of Pharmacy-Drug Sciences, University of Studies of Bari Aldo Moro, Via E. Orabona n. 4, Bari 70126, Italy

³ Pharmacognosy Research Laboratories & Herbal Analysis Services, University of Greenwich, Central Avenue, Charham-Maritime, Kent ME4 4TB, UK

Molecules 2016, 21(11), 1530; https://doi.org/10.3390/molecules21111530 - 13 Nov 2016

Cited by 157 | Viewed by 18990

Abstract

Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs [...] Read more.

Citrus limonoids (CLs) are a group of highly oxygenated terpenoid secondary metabolites found mostly in the seeds, fruits and peel tissues of citrus fruits such as lemons, limes, oranges, pumellos, grapefruits, bergamots, and mandarins. Represented by limonin, the aglycones and glycosides of CLs have shown to display numerous pharmacological activities including anticancer, antimicrobial, antioxidant, antidiabetic and insecticidal among others. In this review, the chemistry and pharmacology of CLs are systematically scrutinised through the use of medicinal chemistry tools and structure-activity relationship approach. Synthetic derivatives and other structurally-related limonoids from other sources are include in the analysis. With the focus on literature in the past decade, the chemical classification of CLs, their physico-chemical properties as drugs, their biosynthesis and enzymatic modifications, possible ways of enhancing their biological activities through structural modifications, their ligand efficiency metrics and systematic graphical radar plot analysis to assess their developability as drugs are among those discussed in detail. Full article

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11 pages, 1339 KiB

Open AccessArticle

Natural Deep Eutectic Solvents (NADES) as a Tool for Bioavailability Improvement: Pharmacokinetics of Rutin Dissolved in Proline/Glycine after Oral Administration in Rats: Possible Application in Nutraceuticals

by Marta Faggian¹, Stefania Sut¹, Beatrice Perissutti²

, Valeria Baldan¹, Iztok Grabnar³ and Stefano Dall’Acqua^1,*

¹ Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy

² Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy

³ Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, SI-1000 Ljubljana, Slovenia

Molecules 2016, 21(11), 1531; https://doi.org/10.3390/molecules21111531 - 14 Nov 2016

Cited by 187 | Viewed by 18078

Abstract

There is a need for innovation in plant-derived pharmaceuticals, food supplements and nutraceutical products regarding the use of more eco-sustainable solvents for their extraction. Furthermore, the poor oral bioavailability of several phytochemicals with health promoting effects stimulates the research in the field of [...] Read more.

There is a need for innovation in plant-derived pharmaceuticals, food supplements and nutraceutical products regarding the use of more eco-sustainable solvents for their extraction. Furthermore, the poor oral bioavailability of several phytochemicals with health promoting effects stimulates the research in the field of pharmaceutical formulations. Natural Deep Eutectic Solvents (NADES) are formed by natural compounds, and can be considered as future solvents being especially useful for the preparation of nutraceuticals and food-grade extracts. In this paper various NADES were prepared using sugars, aminoacids and organic acids. Rutin (quercetin-3-O-α-l-rhamnopyranosyl-(1→6))-β-d-glucopyranose) was used as a model compound to study NADES. Moreover, the effect of various eutectic mixtures on rutin’s water solubility was studied. Proline/glutamic acid (2:1) and proline/choline chloride (1:1) mixtures have a solubility comparable to ethanol. The proline/glutamic acid (2:1) eutectic containing rutin was used in a pharmacokinetic study in Balb/c mice while bioavailability was compared to oral dosing of water suspension. Plasmatic levels of rutin were measured by HPLC-MS/MS showing increased levels and longer period of rutin permanence in plasma of NADES treated animals. This paper reports the possible use of non-toxic NADES for pharmaceutical and nutraceutical preparations. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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8 pages, 2693 KiB

Open AccessArticle

One Pot Single Step Synthesis and Biological Evaluation of Some Novel Bis(1,3,4-thiadiazole) Derivatives as Potential Cytotoxic Agents

by Sobhi M. Gomha¹

, Nabila A. Kheder^1,2, Abdou O. Abdelhamid¹

and Yahia N. Mabkhot^3,*

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

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia

³ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2016, 21(11), 1532; https://doi.org/10.3390/molecules21111532 - 15 Nov 2016

Cited by 64 | Viewed by 6003

Abstract

A novel series of bis(1,3,4-thiadiazole) derivatives were synthesized in one step methodology with good yields by condensation reaction between bis-hydrazonoyl chloride 1 and various reagents. The structures of the prepared compounds were confirmed by spectral data (IR, NMR, and MS), and [...] Read more.

A novel series of bis(1,3,4-thiadiazole) derivatives were synthesized in one step methodology with good yields by condensation reaction between bis-hydrazonoyl chloride 1 and various reagents. The structures of the prepared compounds were confirmed by spectral data (IR, NMR, and MS), and elemental analysis. The anticancer activity against human breast carcinoma (MCF-7) cancer cell lines was evaluated in MTT assay. The results revealed that the bis-thiadiazole derivatives 5c,d, 7b,c and 9c had higher antitumor activity than the standard drug Imatinib. Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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17 pages, 5398 KiB

Open AccessArticle

Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines

by Luis Sánchez-Sánchez¹, María Guadalupe Hernández-Linares^2,*, María L. Escobar³

, Hugo López-Muñoz¹, Edgar Zenteno^4,5, María A. Fernández-Herrera⁶, Gabriel Guerrero-Luna^2,7, Alan Carrasco-Carballo^2,7

and Jesús Sandoval-Ramírez⁷

¹ Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230 Ciudad de México, Mexico

² Laboratorio de Investigación, Jardín Botánico Universitario, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Pue., Mexico

³ Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510 Ciudad de México, Mexico

⁴ Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 Ciudad de México, Mexico

⁵ Centro de Investigación UNAM-UABJO, 68120 Oaxaca, Oax., Mexico

⁶ Departamento de Física Aplicada, Centro de Investigación y de Estudios Avanzados—Unidad Mérida, km 6 Antigua Carretera a Progreso, Cordemex, 97310 Mérida, Yuc., Mexico

⁷ Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Pue., Mexico

Molecules 2016, 21(11), 1533; https://doi.org/10.3390/molecules21111533 - 14 Nov 2016

Cited by 25 | Viewed by 7228

Abstract

Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report [...] Read more.

Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells. These derivatives were synthesized from the steroidal sapogenin diosgenin in good yields. The in vitro assays show that the steroidal oximes show significant antiproliferative activity compared to the one observed for diosgenin. Cell proliferation, cell death, and the cytotoxic effects were determined in both cervical cancer cells and human lymphocytes. The cancer cells showed apoptotic morphology and an increased presence of active caspase-3, providing the notion of a death pathway in the cell. Significantly, the steroidal oximes did not exert a cytotoxic effect on lymphocytes. Full article

(This article belongs to the Special Issue Women in Organic Chemistry)

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7 pages, 2411 KiB

Open AccessArticle

Oxoisoaporphine as Potent Telomerase Inhibitor

by Zu-Zhuang Wei^†, Qi-Pin Qin^†, Jia-Nian Chen and Zhen-Feng Chen^*

¹ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1534; https://doi.org/10.3390/molecules21111534 - 14 Nov 2016

Cited by 14 | Viewed by 4838

Abstract

Two compounds previously isolated from traditional Chinese medicine, Menispermum dauricum (DC), 6-hydroxyl-oxoisoaporphine (H-L^a), and 4,6-di(2-pyridinyl)benzo[h]isoindolo[4,5,6-de]quinolin-8(5H)-one (H-L^b), were known to have in vitro antitumor activity and to selectively bind human telomeric, c-myc, and bcl-2 [...] Read more.

Two compounds previously isolated from traditional Chinese medicine, Menispermum dauricum (DC), 6-hydroxyl-oxoisoaporphine (H-L^a), and 4,6-di(2-pyridinyl)benzo[h]isoindolo[4,5,6-de]quinolin-8(5H)-one (H-L^b), were known to have in vitro antitumor activity and to selectively bind human telomeric, c-myc, and bcl-2 G-quadruplexes (G4s). In this study, the binding properties of these two compounds to telomerase were investigated through molecular docking and telomeric repeat amplication protocol and silver staining assay (TRAP-silver staining assay). The binding energies bound to human telomerase RNA were calculated by molecular docking to be −6.43 and −9.76 kcal/mol for H-L^a and H-L^b, respectively. Compared with H-L^a, the ligand H-L^b more strongly inhibited telomerase activity in the SK-OV-3 cells model. Full article

(This article belongs to the Section Medicinal Chemistry)

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35 pages, 9631 KiB

Open AccessReview

The Reciprocal Principle of Selectand-Selector-Systems in Supramolecular Chromatography †

by Volker Schurig^†

¹ Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany

^† This contribution is dedicated to Professor Stig Allenmark at his 80th anniversary.

Molecules 2016, 21(11), 1535; https://doi.org/10.3390/molecules21111535 - 15 Nov 2016

Cited by 21 | Viewed by 7287

Abstract

In selective chromatography and electromigration methods, supramolecular recognition of selectands and selectors is due to the fast and reversible formation of association complexes governed by thermodynamics. Whereas the selectand molecules to be separated are always present in the mobile phase, the selector employed [...] Read more.

In selective chromatography and electromigration methods, supramolecular recognition of selectands and selectors is due to the fast and reversible formation of association complexes governed by thermodynamics. Whereas the selectand molecules to be separated are always present in the mobile phase, the selector employed for the separation of the selectands is either part of the stationary phase or is added to the mobile phase. By the reciprocal principle, the roles of selector and selectand can be reversed. In this contribution in honor of Professor Stig Allenmark, the evolution of the reciprocal principle in chromatography is reviewed and its advantages and limitations are outlined. Various reciprocal scenarios, including library approaches, are discussed in efforts to optimize selectivity in separation science. Full article

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

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16 pages, 2250 KiB

Open AccessArticle

Organ- and Growing Stage-Specific Expression of Solanesol Biosynthesis Genes in Nicotiana tabacum Reveals Their Association with Solanesol Content

by Ning Yan¹, Hongbo Zhang¹, Zhongfeng Zhang¹, John Shi², Michael P. Timko³

, Yongmei Du¹, Xinmin Liu¹ and Yanhua Liu^1,*

¹ Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao 266101, China

² Guelph Food Research Center, Agriculture and Agri-Food Canada, Guelph, ON N1G 5C9, Canada

³ Department of Biology, University of Virginia, Charlottesville, VA 22904, USA

Molecules 2016, 21(11), 1536; https://doi.org/10.3390/molecules21111536 - 15 Nov 2016

Cited by 13 | Viewed by 6697

Abstract

Solanesol is a noncyclic terpene alcohol that is composed of nine isoprene units and mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). In the present study, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify putative solanesol [...] Read more.

Solanesol is a noncyclic terpene alcohol that is composed of nine isoprene units and mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). In the present study, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify putative solanesol biosynthesis genes. Six 1-deoxy-d-xylulose 5-phosphate synthase (DXS), two 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), two 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase (IspD), four 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase (IspE), two 2-C-methyl-d-erythritol 2,4-cyclo-diphosphate synthase (IspF), four 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (IspG), two 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (IspH), six isopentenyl diphosphate isomerase (IPI), and two solanesyl diphosphate synthase (SPS) candidate genes were identified in the solanesol biosynthetic pathway. Furthermore, the two N. tabacum SPS proteins (NtSPS1 and NtSPS2), which possessed two conserved aspartate-rich DDxxD domains, were highly homologous with SPS enzymes from other solanaceous plant species. In addition, the solanesol contents of three organs and of leaves from four growing stages of tobacco plants corresponded with the distribution of chlorophyll. Our findings provide a comprehensive evaluation of the correlation between the expression of different biosynthesis genes and the accumulation of solanesol, thus providing valuable insight into the regulation of solanesol biosynthesis in tobacco. Full article

(This article belongs to the Special Issue Selected papers from 2nd International Symposium on Phytochemicals in Medicine and Food (2-ISPMF, Fuzhou, 2017))

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12 pages, 3592 KiB

Open AccessArticle

Comparison of Chemical Compositions in Pseudostellariae Radix from Different Cultivated Fields and Germplasms by NMR-Based Metabolomics

by Yujiao Hua^†, Ya Hou^†, Shengnan Wang, Yang Ma, Zixiu Liu, Lisi Zou, Xunhong Liu^*, Yiyuan Luo and Juanxiu Liu

¹ College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1538; https://doi.org/10.3390/molecules21111538 - 15 Nov 2016

Cited by 12 | Viewed by 5706

Abstract

Pseudostellariae Radix (PR) is an important traditional Chinese medicine (TCM), which is consumed commonly for its positive health effects. However, the chemical differences of PR from different cultivated fields and germplasms are still unknown. In order to comprehensively compare the chemical compositions of [...] Read more.

Pseudostellariae Radix (PR) is an important traditional Chinese medicine (TCM), which is consumed commonly for its positive health effects. However, the chemical differences of PR from different cultivated fields and germplasms are still unknown. In order to comprehensively compare the chemical compositions of PR from different cultivated fields, in this study, ¹H-NMR-based metabolomics coupled with high performance liquid chromatography (HPLC) were used to investigate the different metabolites in PR from five germplasms (jr, zs1, zs2, sb, and xc) cultivated in traditional fields (Jurong, Jiangsu, JSJR) and cultivated fields (Zherong, Fujian, FJZR). A total of 34 metabolites were identified based on ¹H-NMR data, and fourteen of them were found to be different in PR from JSJR and FJZR. The relative contents of alanine, lactate, lysine, taurine, sucrose, tyrosine, linolenic acid, γ-aminobutyrate, and hyperoside in PR from JSJR were higher than that in PR from FJZR, while PR from FJZR contained higher levels of glutamine, raffinose, xylose, unsaturated fatty acid, and formic acid. The contents of Heterophyllin A and Heterophyllin B were higher in PR from FJZR. This study will provide the basic information for exploring the influence law of ecological environment and germplasm genetic variation on metabolite biosynthesis of PR and its quality formation mechanism. Full article

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16 pages, 1853 KiB

Open AccessArticle

A Green Approach for Allylations of Aldehydes and Ketones: Combining Allylborate, Mechanochemistry and Lanthanide Catalyst

by Viviane P. De Souza, Cristiane K. Oliveira, Thiago M. De Souza, Paulo H. Menezes, Severino Alves, Ricardo L. Longo and Ivani Malvestiti^*

Departamento de Química Fundamental—Universidade Federal de Pernambuco, Av. Jornalista Aníbal Fernandes, s/n—Cidade Universitária, Recife—PE 50740-560, Brazil

Molecules 2016, 21(11), 1539; https://doi.org/10.3390/molecules21111539 - 16 Nov 2016

Cited by 8 | Viewed by 5617

Abstract

Secondary and tertiary alcohols synthesized via allylation of aldehydes and ketones are important compounds in bioactive natural products and industry, including pharmaceuticals. Development of a mechanochemical method using potassium allyltrifluoroborate salt and water, to successfully perform the allylation of aromatic and aliphatic carbonyl [...] Read more.

Secondary and tertiary alcohols synthesized via allylation of aldehydes and ketones are important compounds in bioactive natural products and industry, including pharmaceuticals. Development of a mechanochemical method using potassium allyltrifluoroborate salt and water, to successfully perform the allylation of aromatic and aliphatic carbonyl compounds is reported for the first time. By controlling the grinding parameters, the methodology can be selective, namely, very efficient for aldehydes and ineffective for ketones, but by employing lanthanide catalysts, the reactions with ketones can become practically quantitative. The catalyzed reactions can also be performed under mild aqueous stirring conditions. Considering the allylation agent and its by-products, aqueous media, energy efficiency and use of catalyst, the methodology meets most of the green chemistry principles. Full article

(This article belongs to the Section Green Chemistry)

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8 pages, 1649 KiB

Open AccessArticle

Theoretical Study on the Second Hyperpolarizailities of Oligomeric Systems Composed of Carbon and Silicon π-Structures

by Hiroshi Matsui, Takanori Nagami, Shota Takamuku, Soichi Ito, Yasutaka Kitagawa

and Masayoshi Nakano^*

Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan

Molecules 2016, 21(11), 1540; https://doi.org/10.3390/molecules21111540 - 15 Nov 2016

Cited by 2 | Viewed by 4742

Abstract

To explore the prospect of molecules involving silicon-silicon multiple bonds as nonlinear optical molecular systems, the relationship between the structure and the second hyperpolarizabilities γ of the oligomeric systems composed of carbon and silicon π-structures is investigated using the density functional theory method. [...] Read more.

To explore the prospect of molecules involving silicon-silicon multiple bonds as nonlinear optical molecular systems, the relationship between the structure and the second hyperpolarizabilities γ of the oligomeric systems composed of carbon and silicon π-structures is investigated using the density functional theory method. It is found that these compounds indicate intramolecular charge transfer (ICT) from the silicon units to the carbon units together with nonzero diradical characters. The γ values of these compounds are shown to be 2–13 times as large as those of the carbon analogs. Although asymmetric carbon and silicon π-systems exhibit comparable enhancement to the corresponding symmetric systems, donor-π-donor structures exhibit remarkable enhancement of γ despite of their both-end short silicon π-chain moieties (donor units). Further analysis using the odd electron and γ densities clarifies that the intermediate diradical character also contributes to the enhancement of γ. These results predict that even short π-conjugated silicone moieties can cause remarkable enhancement of γ by introducing them into π-conjugated hydrocarbon structures. Full article

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

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10 pages, 1628 KiB

Open AccessCommunication

Photo Racemization and Polymerization of (R)-1,1′-Bi(2-naphthol)

by Zhaoming Zhang¹, Yue Wang¹ and Tamaki Nakano^1,2,*

¹ Macromolecular Science Research Division, Institute for Catalysis and Graduate School of Chemical Sciences and Engineering, Hokkaido University, N21 W10, Kita-ku, Sapporo 001-0021, Japan

² Integrated Research Consortium on Chemical Sciences (IRCCS), Institute for Catalysis, Hokkaido University, N21 W10, Kita-ku, Sapporo 001-0021, Japan

Molecules 2016, 21(11), 1541; https://doi.org/10.3390/molecules21111541 - 16 Nov 2016

Cited by 17 | Viewed by 8089

Abstract

(R)-1,1’-Bi(2-naphthol) ((R)-BINOL) in an acetonitrile solution lost optical activity upon irradiation with an Hg–Xe lamp. HPLC resolution of the product indicated that (R)-BINOL was racemized upon irradiation, and SEC analysis suggested that a polymeric product was formed [...] Read more.

(R)-1,1’-Bi(2-naphthol) ((R)-BINOL) in an acetonitrile solution lost optical activity upon irradiation with an Hg–Xe lamp. HPLC resolution of the product indicated that (R)-BINOL was racemized upon irradiation, and SEC analysis suggested that a polymeric product was formed in the course of racemization. It is proposed that polymerization of BINOL can occur before it is racemized and that a unit in a polymer derived from BINOL may lose its optical activity afterwards due to in-chain racemization and/or reduction. The polymeric products seem to consist not only of BINOL residues but also of residues derived from acetonitrile as well as those derived through reduction of BINOL. Full article

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

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12 pages, 2567 KiB

Open AccessArticle

Deprotection Reagents in Fmoc Solid Phase Peptide Synthesis: Moving Away from Piperidine?

by Omar F. Luna¹, Johana Gomez², Constanza Cárdenas^1,2

, Fernando Albericio^3,4,5

, Sergio H. Marshall^1,2,6 and Fanny Guzmán^1,2,*

¹ Fraunhofer Chile Research, Santiago 7550296, Chile

² Núcleo Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile

³ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of Barcelona, Barcelona 08028, Spain

⁴ Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain

⁵ School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa

⁶ Instituto de Biología, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile

Molecules 2016, 21(11), 1542; https://doi.org/10.3390/molecules21111542 - 15 Nov 2016

Cited by 76 | Viewed by 24598

Abstract

The deprotection step is crucial in order to secure a good quality product in Fmoc solid phase peptide synthesis. 9-Fluorenylmethoxycarbonyl (Fmoc) removal is achieved by a two-step mechanism reaction favored by the use of cyclic secondary amines; however, the efficiency of the reaction [...] Read more.

The deprotection step is crucial in order to secure a good quality product in Fmoc solid phase peptide synthesis. 9-Fluorenylmethoxycarbonyl (Fmoc) removal is achieved by a two-step mechanism reaction favored by the use of cyclic secondary amines; however, the efficiency of the reaction could be affected by side reactions and by-product formation. Several aspects have to be taken into consideration when selecting a deprotection reagent: its physicochemical behavior, basicity (pKa) and polarity, concentration, and time of reaction, toxicity and disposability of residues and, finally, availability of reagents. This report presents a comparison of the performance of three strategies for deprotection using microwave-assisted Fmoc peptide synthesis. Four peptide sequences were synthesized using Rink amide resin with a Liberty Blue™ automated synthesizer and 4-methylpiperidine (4MP), piperidine (PP), and piperazine (PZ) as Fmoc removal reagents. In the first instance all three reagents behaved similarly. A detailed analysis showed a correlation between the hydrophobicity and size of the peptide with the yield and purity of the obtained product. The three reagents are interchangeable, and replacement of piperidine could be advantageous regarding toxicity and reagent handling. Full article

(This article belongs to the Section Organic Chemistry)

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31 pages, 1636 KiB

Open AccessArticle

Discovery of a Flexible Triazolylbutanoic Acid as a Highly Potent Uric Acid Transporter 1 (URAT1) Inhibitor

by He Tian^1,2, Wei Liu², Zhixing Zhou², Qian Shang², Yuqiang Liu², Yafei Xie², Changying Liu², Weiren Xu², Lida Tang², Jianwu Wang^1,* and Guilong Zhao^2,*

¹ School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China

² Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China

Molecules 2016, 21(11), 1543; https://doi.org/10.3390/molecules21111543 - 16 Nov 2016

Cited by 22 | Viewed by 7884

Abstract

In order to systematically explore and understand the structure–activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH₂, 18 compounds (1a–1r) were designed, synthesized and [...] Read more.

In order to systematically explore and understand the structure–activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH₂, 18 compounds (1a–1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC₅₀ = 0.23 μM against human URAT1 for 1q vs 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 1350 KiB

Open AccessArticle

Synthesis, Characterization, and Anti-Inflammatory Activities of Methyl Salicylate Derivatives Bearing Piperazine Moiety

by Jingfen Li^1,†, Yong Yin^2,†, Lisheng Wang², Pengyun Liang², Menghua Li², Xu Liu², Lichuan Wu^2,* and Hua Yang^2,*

¹ Department of Life Science, Huzhou Teachers’ College, Huzhou 313000, China

² School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1544; https://doi.org/10.3390/molecules21111544 - 23 Nov 2016

Cited by 18 | Viewed by 8322

Abstract

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that [...] Read more.

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 2595 KiB

Open AccessArticle

Diphenylcarbene Protected by Four ortho-Iodine Groups: An Unusually Persistent Triplet Carbene

by Katsuyuki Hirai^1,*, Kana Bessho², Kosaku Tsujita² and Toshikazu Kitagawa^2,*

¹ Community-University Research Cooperation Center, Mie University, Tsu, Mie 514-8507, Japan

² Department of Chemistry for Materials, Graduate School of Engineering, Mie University, Tsu, Mie 514-8507, Japan

Molecules 2016, 21(11), 1545; https://doi.org/10.3390/molecules21111545 - 15 Nov 2016

Cited by 6 | Viewed by 6206

Abstract

Diphenyldiazomethane with four iodine groups at the ortho positions and two tert-butyl groups at the para positions, i.e., bis(4-tert-butyl-2,6-diiodophenyl)diazomethane (1a-N₂), was synthesized as a sterically hindered triplet carbene precursor. Irradiation of 1a-N₂ in solution [...] Read more.

Diphenyldiazomethane with four iodine groups at the ortho positions and two tert-butyl groups at the para positions, i.e., bis(4-tert-butyl-2,6-diiodophenyl)diazomethane (1a-N₂), was synthesized as a sterically hindered triplet carbene precursor. Irradiation of 1a-N₂ in solution effectively generated the corresponding triplet diphenylcarbene ³1a, which was characterized by UV-vis spectroscopy at low temperature, along with laser flash photolysis techniques at room temperature. The UV-vis spectrum of ³1a was obtained by irradiating 1a-N₂ in a 2-methyltetrahydrofuran matrix at 77 K. The ESR spectrum showed no triplet carbene signals, while a radical species was observed at the anticipated temperature of the decomposition of triplet carbene ³1a. Transient absorption bands ascribable to ³1a were observed by laser flash photolysis of 1a-N₂ in a degassed benzene solution and decayed very slowly with a second-order rate constant (2k/εl) of 5.5 × 10⁻³·s⁻¹. Steady-state irradiation of 1a-N₂ in degassed benzene afforded 9,10-diarylphenanthrene derivative 2a in a 31% yield. Triplet carbene ³1a was also trapped by either oxygen (k_O2 = 6.5 × 10⁵ M⁻¹·s⁻¹) or 1,4-cyclohexadiene (k_CHD = 1.5 M⁻¹·s⁻¹) to afford the corresponding ketone 1a-O or the diarylmethane 1a-H₂. The carbene was shown to be much less reactive than the triplet diphenylcarbene that is protected by two ortho-iodo and two ortho-bromo groups, ³1b. Full article

(This article belongs to the Special Issue Cutting-Edge Organic Chemistry in Japan)

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14 pages, 7758 KiB

Open AccessArticle

Unfolding/Refolding Study on Collagen from Sea Cucumber Based on 2D Fourier Transform Infrared Spectroscopy

by Lei Qin^1,2, Jing-Ran Bi^1,2,3, Dong-Mei Li^1,2,*, Meng Dong¹, Zi-Yuan Zhao¹, Xiu-Ping Dong^1,2, Da-Yong Zhou^1,2 and Bei-Wei Zhu^1,2,*

¹ School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China

² National Engineering Research Center of Seafood, Dalian 116034, China

³ School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China

Molecules 2016, 21(11), 1546; https://doi.org/10.3390/molecules21111546 - 16 Nov 2016

Cited by 17 | Viewed by 5806

Abstract

We aimed to explore the differences of thermal behaviors between insoluble collagen fibrils (ICFs) and pepsin-solubilized collagens (PSCs) from sea cucumber Stichopus japonicus. The unfolding/refolding sequences of secondary structures of ICFs and PSCs during the heating and cooling cycle (5 → 70 [...] Read more.

We aimed to explore the differences of thermal behaviors between insoluble collagen fibrils (ICFs) and pepsin-solubilized collagens (PSCs) from sea cucumber Stichopus japonicus. The unfolding/refolding sequences of secondary structures of ICFs and PSCs during the heating and cooling cycle (5 → 70 → 5 °C) were identified by Fourier transform infrared spectrometry combined with curve-fitting and 2D correlation techniques. ICFs showed a higher proportion of α-helical structures and higher thermostability than PSCs, and thus had more-stable triple helical structures. The sequences of changes affecting the secondary structures during heating were essentially the same between ICFs and PSCs. In all cases, α-helix structure was the most important conformation and it disappeared to form a β-sheet structure. In the cooling cycle, ICFs showed a partially refolding ability, and the proportion of β-sheet structure rose before the increasing proportion of α-helix structure. PSCs did not obviously refold during the cooling stage. Full article

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9 pages, 2990 KiB

Open AccessArticle

Fractional CO₂ Laser Pretreatment Facilitates Transdermal Delivery of Two Vitamin C Derivatives

by Chien-Yu Hsiao^1,2,3, Hsin-Ching Sung^3,4, Sindy Hu^3,5,6, Yau-Li Huang^3,5,6 and Chun-Hsun Huang^2,3,6,*

¹ Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan

² Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33301, Taiwan

³ Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

⁴ Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁵ College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁶ Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan

Molecules 2016, 21(11), 1547; https://doi.org/10.3390/molecules21111547 - 16 Nov 2016

Cited by 10 | Viewed by 6024

Abstract

Background: Topical vitamin C derivatives have been used to treat melasma and used as a skin whitener. The aim of this study was to compare skin histology and permeation of l-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1) and magnesium l-ascorbic acid-2-phosphate (MAP-2) [...] Read more.

Background: Topical vitamin C derivatives have been used to treat melasma and used as a skin whitener. The aim of this study was to compare skin histology and permeation of l-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1) and magnesium l-ascorbic acid-2-phosphate (MAP-2) after fractional CO₂ laser pretreatment. Methods: The effect of fractional laser treatment on porcine skin was examined by scanning electron microscopy and confocal laser scanning electron microscopy. The effect of fractional CO₂ laser treatment of different fluencies and pass numbers on transdermal flux of the two vitamin C derivatives through porcine skin was examined in vitro using a Franz diffusion chamber. Results: Fluxes of MAP-1 and MAP-2 across fractional CO₂ laser-treated (5 W) skin were eight- to 13-fold, and 20- to 22-fold higher, respectively, than the fluxes of these compounds across intact skin. Fluxes of MAP-1 and MAP-2 across fractional CO₂ laser-treated (9 W) skin were 14- to 19-fold, and 30- to 42-fold higher, respectively, than their fluxes across intact skin. Conclusion: Fractional CO₂ laser treatment is an effective way of delivering vitamin C derivatives into the skin. Full article

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

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13 pages, 1689 KiB

Open AccessArticle

Oxidatively Locked [Co₂L₃]⁶⁺ Cylinders Derived from Bis(bidentate) 2-Pyridyl-1,2,3-triazole “Click” Ligands: Synthesis, Stability, and Antimicrobial Studies

by Roan A. S. Vasdev¹, Dan Preston¹, Synøve Ø. Scottwell¹, Heather J. L. Brooks², James D. Crowley^1,*

and Michael P. Schramm^3,*

¹ Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9016, Otago, New Zealand

² Department of Microbiology and Immunology, University of Otago, P.O. Box 56, 720 Cumberland Street, Dunedin 9054, Otago, New Zealand

³ Department of Chemistry and Biochemistry, California State University, Long Beach, 1250 Bellflower Boulevard, Long Beach, CA 90840-9507, USA

Molecules 2016, 21(11), 1548; https://doi.org/10.3390/molecules21111548 - 16 Nov 2016

Cited by 24 | Viewed by 6382

Abstract

A small family of [Co₂(L_pytrz)₃]⁶⁺ cylinders was synthesised from bis(bidentate) 2-pyridyl-1,2,3-triazole “click” ligands (L_pytrz) through an “assembly-followed-by-oxidation” method. The cylinders were characterised using ¹H, ¹³C, and DOSY NMR, IR, and [...] Read more.

A small family of [Co₂(L_pytrz)₃]⁶⁺ cylinders was synthesised from bis(bidentate) 2-pyridyl-1,2,3-triazole “click” ligands (L_pytrz) through an “assembly-followed-by-oxidation” method. The cylinders were characterised using ¹H, ¹³C, and DOSY NMR, IR, and UV-Vis spectroscopies, along with electrospray ionisation mass spectrometry (ESMS). Stability studies were conducted in dimethyl sulfoxide (DMSO) and D₂O. In contrast to similar, previously studied, [Fe₂(L_pytrz)₃]⁴⁺ helicates the more kinetically inert [Co₂(L_pytrz)₃]⁶⁺ systems proved stable (over a period of days) when exposed to DMSO and were even more stable in D₂O. The triply stranded [Co₂(L_pytrz)₃]⁶⁺ systems and the corresponding “free” ligands were tested for antimicrobial activity in vitro against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) microorganisms. Agar-based disk diffusion and Mueller–Hinton broth micro-dilution assays showed that the [Co₂(L_pytrz)₃]⁶⁺ cylinders were not active against either strain of bacteria. It is presumed that a high charge of the [Co₂(L_pytrz)₃]⁶⁺ cylinders is preventing them from crossing the bacterial cell membranes, rendering the compounds biologically inactive. Full article

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

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11 pages, 7369 KiB

Open AccessArticle

Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies

by Jihui Zhao^†

, Xianghua Piao^†, Xiaoqin Shi, Aiyong Si, Yongtai Zhang and Nianping Feng^*

¹ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

^† These authors contribute equally to this work.

Molecules 2016, 21(11), 1549; https://doi.org/10.3390/molecules21111549 - 17 Nov 2016

Cited by 34 | Viewed by 5837 | Correction

Abstract

Nanostructured lipid carriers (NLC) exhibit high skin targeting efficiency and good safety. They are promising vehicles for topical drug delivery. This study aims to increase the skin distribution of podophyllotoxin (POD) by incorporating it into NLCs. Two kinds of POD-loaded NLCs (POD-NLCs)—POD-NLC_formulation [...] Read more.

Nanostructured lipid carriers (NLC) exhibit high skin targeting efficiency and good safety. They are promising vehicles for topical drug delivery. This study aims to increase the skin distribution of podophyllotoxin (POD) by incorporating it into NLCs. Two kinds of POD-loaded NLCs (POD-NLCs)—POD-NLC_{formulation 1} and POD-NLC_{formulation 2}—were prepared and characterized. Their skin targeting efficiencies were compared by conducting in vitro and in vivo experiments. Obviously smaller mean particle size was observed for POD-NLC_{formulation 1} (106 nm) than POD-NLC_{formulation 2} (219 nm), whereas relatively low POD loadings (less than 0.5%) were observed for both POD-NLC_{formulation 1} (0.33%) and POD-NLC_{formulation 2} (0.49%). Significantly higher in vitro and in vivo rat skin deposit amounts of POD (p ˂ 0.01) were detected after the topical application of POD-NLC_{formulation 1} compared to POD-NLC_{formulation 2}. To visualize the skin distribution behavior of hydrophobic active pharmaceutical ingredients (APIs) when NLCs were used as carriers, POD was replaced with Nile red (NR—a hydrophobic fluorescent probe), and the distribution behavior of NR-NLC_{formulation 1} and NR-NLC_{formulation 2} in rat skin in vivo was observed using confocal laser scanning microscopy (CLSM). Higher fluorescent intensity was observed in rat skin after the topical application of NR-NLC_{formulation 1} than NR-NLC_{formulation 2}, suggesting that higher skin targeting efficiency might be obtained when NLCs with smaller mean particle size were used as carriers for hydrophobic APIs. This result was in accordance with those of skin distribution evaluation experiments of POD-NLCs. Skin irritation property of POD-NLC_{formulation 1} was investigated and no irritation was observed in intact or damaged rabbit skin, suggesting it is safe for topical use. Our results validated the safety of NLCs when applied topically. More importantly, mean particle size might be an important parameter for formulation optimization when NLCs are used as carriers for hydrophobic APIs for topical application, considering that their loading is relatively low. Full article

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

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5 pages, 1285 KiB

Open AccessCorrection

Correction: Griffith, D.M., et al. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells. Molecules 2016, 21, 949

by Aoife M. McKeon¹, Alan Egan², Jay Chandanshive¹, Helena McMahon² and Darren M. Griffith^1,*

¹ Centre for Synthesis and Chemical Biology, Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2 D02 YN77, Ireland

² Shannon ABC, South Campus, IT Tralee, Clash, Tralee, Co., Kerry V92 CX88, Ireland

Molecules 2016, 21(11), 1550; https://doi.org/10.3390/molecules21111550 - 17 Nov 2016

Cited by 2 | Viewed by 3667

Abstract

n/a Full article

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14 pages, 1792 KiB

Open AccessArticle

Biogenesis of Triterpene Dimers from Orthoquinones Related to Quinonemethides: Theoretical Study on the Reaction Mechanism

by Mariana Quesadas-Rojas¹, Gonzalo J. Mena-Rejón^1,*, David Cáceres-Castillo¹, Gabriel Cuevas² and Ramiro F. Quijano-Quiñones^1,*

¹ Facultad de Química, Universidad Autónoma de Yucatán, Calle 43 No. 613, Col. Inalambrica, Mérida, Yucatán, C.P. 97069, Mexico

² Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Ciudad de México, C.P. 04510, Mexico

Molecules 2016, 21(11), 1551; https://doi.org/10.3390/molecules21111551 - 17 Nov 2016

Cited by 5 | Viewed by 5258

Abstract

The biogenetic origin of triterpene dimers from the Celastraceae family has been proposed as assisted hetero-Diels-Alder reaction (HDA). In this work, computational calculation of HDA between natural quinonemethides (tingenone and isopristimerol) and hypothetical orthoquinones has been performed at the M06-2X/6-31G(d) level of theory. [...] Read more.

The biogenetic origin of triterpene dimers from the Celastraceae family has been proposed as assisted hetero-Diels-Alder reaction (HDA). In this work, computational calculation of HDA between natural quinonemethides (tingenone and isopristimerol) and hypothetical orthoquinones has been performed at the M06-2X/6-31G(d) level of theory. We have located all the HDA transition states supporting the biogenetic route via HDA cycloadditions. We found that all reactions take place through a concerted inverse electron demand and asynchronous mechanism. The enzymatic assistance for dimer formation was analyzed in terms of the calculated transition state energy barrier. Full article

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14 pages, 953 KiB

Open AccessArticle

Chemoenzymatic Synthesis of trans-β-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures

by Andrzej Skrobiszewski^1,*, Witold Gładkowski¹, Gabriela Maciejewska² and Czesław Wawrzeńczyk¹

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

² Central Laboratory of the Instrumental Analysis, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, Wrocław 50-370, Poland

Molecules 2016, 21(11), 1552; https://doi.org/10.3390/molecules21111552 - 23 Nov 2016

Cited by 5 | Viewed by 5934

Abstract

Two novel and convenient routes to obtain enantiomerically enriched trans-β-aryl-δ-hydroxy-γ-lactones 5a–d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters 4a–d derived from enzymatically resolved allyl alcohols 1a [...] Read more.

Two novel and convenient routes to obtain enantiomerically enriched trans-β-aryl-δ-hydroxy-γ-lactones 5a–d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters 4a–d derived from enzymatically resolved allyl alcohols 1a–d, both enantiomers of hydroxylactones 5a–d were synthesized with high enantiomeric excesses (73%–97%). Configurations of the stereogenic centers of the synthesized compounds were assigned based on the mechanism of acidic lactonization of esters 4a–d in the presence of m-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically active trans-β-aryl-δ-hydroxy-γ-lactones 5a–d was lipase-catalyzed kinetic resolution of their racemic mixtures by transesterification with vinyl propionate as the acyl donor. The most efficient enzyme in the screening procedure was lipase B from Candida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a–d and (+)-(4R,5S,6R)-propionates 6a–d, most of them with high enantiomeric excesses (92%–98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee = 89% and 84% for hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give access to both enantiomers of trans-β-aryl-δ-hydroxy-γ-lactones 5a–d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure–biological activity. Full article

(This article belongs to the Section Organic Chemistry)

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15 pages, 1949 KiB

Open AccessArticle

Induction of Laccase, Lignin Peroxidase and Manganese Peroxidase Activities in White-Rot Fungi Using Copper Complexes

by Martina Vrsanska¹, Stanislava Voberkova^1,2, Vratislav Langer³, Dagmar Palovcikova⁴, Amitava Moulick^1,2, Vojtech Adam^1,2 and Pavel Kopel^1,2,*

¹ Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic

² Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00 Brno, Czech Republic

³ Environmental Inorganic Chemistry, Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden

⁴ Department of Forest Protection and Wildlife Management, Faculty of Forestry and Wood Technology, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic

Molecules 2016, 21(11), 1553; https://doi.org/10.3390/molecules21111553 - 17 Nov 2016

Cited by 69 | Viewed by 11541

Abstract

Ligninolytic enzymes, such as laccase, lignin peroxidase and manganese peroxidase, are biotechnologically-important enzymes. The ability of five white-rot fungal strains Daedaleopsis confragosa, Fomes fomentarius, Trametes gibbosa, Trametes suaveolens and Trametes versicolor to produce these enzymes has been studied. Three different [...] Read more.

Ligninolytic enzymes, such as laccase, lignin peroxidase and manganese peroxidase, are biotechnologically-important enzymes. The ability of five white-rot fungal strains Daedaleopsis confragosa, Fomes fomentarius, Trametes gibbosa, Trametes suaveolens and Trametes versicolor to produce these enzymes has been studied. Three different copper(II) complexes have been prepared ((Him)[Cu(im)₄(H₂O)₂](btc)·3H₂O, where im = imidazole, H₃btc = 1,3,5-benzenetricarboxylic acid, [Cu₃(pmdien)₃(btc)](ClO₄)₃·6H₂O) and [Cu₃(mdpta)₃(btc)](ClO₄)₃·4H₂O, where pmdien = N,N,N′,N′′,N′′-pentamethyl-diethylenetriamine and mdpta = N,N-bis-(3-aminopropyl)methyl- amine), and their potential application for laccase and peroxidases induction have been tested. The enzyme-inducing activities of the complexes were compared with that of copper sulfate, and it has been found that all of the complexes are suitable for the induction of laccase and peroxidase activities in white-rot fungi; however, the newly-synthesized complex M1 showed the greatest potential for the induction. With respect to the different copper inducers, this parameter seems to be important for enzyme activity, which depends also on the fungal strains. Full article

(This article belongs to the Section Bioorganic Chemistry)

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20 pages, 3835 KiB

Open AccessArticle

Three-Dimensional Biologically Relevant Spectrum (BRS-3D): Shape Similarity Profile Based on PDB Ligands as Molecular Descriptors

by Ben Hu^1,2, Zheng-Kun Kuang^1,2, Shi-Yu Feng¹, Dong Wang¹, Song-Bing He¹ and De-Xin Kong^1,2,*

¹ State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China

² Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China

Molecules 2016, 21(11), 1554; https://doi.org/10.3390/molecules21111554 - 17 Nov 2016

Cited by 22 | Viewed by 6399

Abstract

The crystallized ligands in the Protein Data Bank (PDB) can be treated as the inverse shapes of the active sites of corresponding proteins. Therefore, the shape similarity between a molecule and PDB ligands indicated the possibility of the molecule to bind with the [...] Read more.

The crystallized ligands in the Protein Data Bank (PDB) can be treated as the inverse shapes of the active sites of corresponding proteins. Therefore, the shape similarity between a molecule and PDB ligands indicated the possibility of the molecule to bind with the targets. In this paper, we proposed a shape similarity profile that can be used as a molecular descriptor for ligand-based virtual screening. First, through three-dimensional (3D) structural clustering, 300 diverse ligands were extracted from the druggable protein–ligand database, sc-PDB. Then, each of the molecules under scrutiny was flexibly superimposed onto the 300 ligands. Superimpositions were scored by shape overlap and property similarity, producing a 300 dimensional similarity array termed the “Three-Dimensional Biologically Relevant Spectrum (BRS-3D)”. Finally, quantitative or discriminant models were developed with the 300 dimensional descriptor using machine learning methods (support vector machine). The effectiveness of this approach was evaluated using 42 benchmark data sets from the G protein-coupled receptor (GPCR) ligand library and the GPCR decoy database (GLL/GDD). We compared the performance of BRS-3D with other 2D and 3D state-of-the-art molecular descriptors. The results showed that models built with BRS-3D performed best for most GLL/GDD data sets. We also applied BRS-3D in histone deacetylase 1 inhibitors screening and GPCR subtype selectivity prediction. The advantages and disadvantages of this approach are discussed. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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10 pages, 2906 KiB

Open AccessReview

Cyclic Glucans Enhance Solubility of Bioavailable Flavonoids

by Seyeon Park

Department of Applied Chemistry, Dongduk Women’s University, Seoul 136-714, Korea

Molecules 2016, 21(11), 1556; https://doi.org/10.3390/molecules21111556 - 16 Nov 2016

Cited by 13 | Viewed by 6136

Abstract

Diverse flavonoids are abundant in dietary food constituents and possess useful biological activities. However, some flavonoids have limited bioavailability due to their low solubility in water. As an important approach to enhance aqueous solubility, inclusion of hydrophobic guest molecules in hydrophilic hosts such [...] Read more.

Diverse flavonoids are abundant in dietary food constituents and possess useful biological activities. However, some flavonoids have limited bioavailability due to their low solubility in water. As an important approach to enhance aqueous solubility, inclusion of hydrophobic guest molecules in hydrophilic hosts such as cyclic glucans has been used. This review summarizes applications of β-cyclodextrin, synthetic β-cyclodextrin derivatives, and newly synthesized derivatives of cyclosophoraoses as complexing agents to enhance the bioavailability of flavonoids such as baicalein, kaempferol, and naphthoflavones. Full article

(This article belongs to the Section Bioorganic Chemistry)

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15 pages, 3299 KiB

Open AccessArticle

The Protective Effects of Icariin against the Homocysteine-Induced Neurotoxicity in the Primary Embryonic Cultures of Rat Cortical Neurons

by Xiao-Ang Li¹, Yuen-Shan HO², Lei Chen³ and W.L. Wendy Hsiao^1,*

¹ State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Av. Wai Long, Taipa, Macau, China

² School of Nursing, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China

³ Department of Genetics, Rutgers University, New Brunswick, NJ 07001, USA

Molecules 2016, 21(11), 1557; https://doi.org/10.3390/molecules21111557 - 22 Nov 2016

Cited by 26 | Viewed by 6111

Abstract

Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer’s disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this [...] Read more.

Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer’s disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau. In addition, icariin downregulated p-extracellular signal-regulated kinase (ERK) which is a kinase targeting tau protein. Furthermore, icariin effectively restored the neuroprotective protein p-Akt that was downregulated by Hcy. We also applied RT² Profiler PCR Arrays focused on genes related to AD and neurotoxicity to examine genes differentially altered by Hcy or icariin. Among the altered genes from the arrays, ADAM9 was downregulated 15 folds in cells treated with Hcy, but markedly restored by icariin. ADAM family, encoded α-secreatase, plays a protective role in AD. Overall, our findings demonstrated that icariin exhibits a strong neuroprotective function and have potential for future development for drug treating neurological disorders, such as AD. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 652 KiB

Open AccessReview

Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis

by Lenka Tomasova^1,2, Piotr Konopelski¹

and Marcin Ufnal^1,*

¹ Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland

² Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 845 05, Slovakia

Molecules 2016, 21(11), 1558; https://doi.org/10.3390/molecules21111558 - 17 Nov 2016

Cited by 131 | Viewed by 14603

Abstract

Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may [...] Read more.

Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide (H₂S) is an important biological mediator in the circulatory system. Thus far, research has focused on the effects of H₂S enzymatically produced by cardiovascular tissues. However, some recent evidence indicates that H₂S released in the colon may also contribute to the control of arterial blood pressure. Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and H₂S is just one among a number of molecules produced by the gut flora. Other gut bacteria-derived compounds that may affect the circulatory system include methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper, we review studies that imply a role of gut microbiota and their metabolites, such as H₂S, in circulatory system homeostasis. Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

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8 pages, 1375 KiB

Open AccessArticle

The C-Terminal O-S Acyl Shift Pathway under Acidic Condition to Propose Peptide-Thioesters

by Bo Mi Kim

Division of Bio-Nanochemistry, Wonkwang University, Iksan 570-749, Korea

Molecules 2016, 21(11), 1559; https://doi.org/10.3390/molecules21111559 - 17 Nov 2016

Cited by 2 | Viewed by 6388

Abstract

Peptide-thioester is a pivotal intermediate for peptide ligation and N-, C-terminal cyclization. In this study, desired pathway and the side products of two C-terminal handles, hydroxyethylthiol (HET) and hydroxypropylthiol (HPT) are described in different conditions as well as kinetic studies. In addition, a [...] Read more.

Peptide-thioester is a pivotal intermediate for peptide ligation and N-, C-terminal cyclization. In this study, desired pathway and the side products of two C-terminal handles, hydroxyethylthiol (HET) and hydroxypropylthiol (HPT) are described in different conditions as well as kinetic studies. In addition, a new mechanism of C-terminal residue racemization is proposed on the basis of differentiation of products derived from the two C-terminal handles in preparing peptide thioesters through an acid-catalyzed tandem thiol switch, first by an intramolecular O-S acyl shift, and then by an intermolecular S-S exchange. Full article

(This article belongs to the Section Organic Chemistry)

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27 pages, 289 KiB

Open AccessReview

Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine

by Letizia Polito^†

, Massimo Bortolotti^†

, Stefania Maiello, Maria Giulia Battelli^*

and Andrea Bolognesi

¹ Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1560; https://doi.org/10.3390/molecules21111560 - 18 Nov 2016

Cited by 51 | Viewed by 9656

Abstract

Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the [...] Read more.

Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the position occupied in traditional medicine by plants from which RIPs have been isolated. The overview starts from the antique age of the Mediterranean area with ancient Egypt, followed by the Greek and Roman classic period. Then, the ancient oriental civilizations of China and India are evaluated. More recently, Unani medicine and European folk medicine are examined. Finally, the African and American folk medicines are taken into consideration. In conclusion, a list of RIP-expressing plants, which have been used in folk medicine, is provided with the geographical distribution and the prescriptions that are recommended by traditional healers. Some final considerations are provided on the present utilization of such herbal treatments, both in developing and developed countries, often in the absence of scientific validation. The most promising prospect for the medicinal use of RIP-expressing plants is the conjugation of purified RIPs to antibodies that recognise tumour antigens for cancer therapy. Full article

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

13 pages, 1432 KiB

Open AccessArticle

Palladium(ii)-Acetylacetonato Complexes with Mesoionic Carbenes: Synthesis, Structures and Their Application in the Suzuki-Miyaura Cross Coupling Reaction

by Lara Hettmanczyk, Bianca Schmid, Stephan Hohloch

and Biprajit Sarkar^*

Institut für Chemie und Biochemie, Anorganische Chemie, Freie Universität Berlin, Fabeckstraße 34-36, Berlin D-14195, Germany

Molecules 2016, 21(11), 1561; https://doi.org/10.3390/molecules21111561 - 17 Nov 2016

Cited by 14 | Viewed by 7826

Abstract

A series of novel palladium(ii) acetylacetonato complexes bearing mesoionic carbenes (MICs) have been synthesized and characterized. The synthesis of the complexes of type (MIC)Pd(acac)I (MIC = 1-mesityl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (1), 1,4-(2,4,6-methyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (2), 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (3); acac = acetylacetonato) [...] Read more.

A series of novel palladium(ii) acetylacetonato complexes bearing mesoionic carbenes (MICs) have been synthesized and characterized. The synthesis of the complexes of type (MIC)Pd(acac)I (MIC = 1-mesityl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene (1), 1,4-(2,4,6-methyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (2), 1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (3); acac = acetylacetonato) via direct metalation starting from the corresponding triazolium iodides and palladium(ii) acetylacetonate is described herein. All complexes were characterized by ¹H- and ¹³C-NMR spectroscopy and high resolution mass spectrometry. Additionally, two of the complexes were characterized by single crystal X-ray crystallography confirming a square-planar coordination geometry of the palladium(ii) center. A delocalized bonding situation was observed within the triazolylidene rings as well as for the acac ligand respectively. Complex 2 was found to be an efficient pre-catalyst for the Suzuki-Miyaura cross coupling reaction between aryl-bromides or -chlorides with phenylboronic acid. Full article

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

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8 pages, 1179 KiB

Open AccessArticle

Antimicrobial Activity of Zabofloxacin against Clinically Isolated Streptococcus pneumoniae

by Hee-Soo Park^1,†, Sang-Hun Oh^2,†, Hye-Shin Kim², Dong-Rack Choi³ and Jin-Hwan Kwak^2,*

¹ School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Korea

² School of Life Science, Handong Global University, 558 Handong-ro, Buk-gu, Pohang 37554, Korea

³ Dong Wha Pharm., Ind. Co. Ltd., Anyang 31041, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1562; https://doi.org/10.3390/molecules21111562 - 17 Nov 2016

Cited by 12 | Viewed by 7023

Abstract

Zabofloxacin is a novel fluoroquinolone agent that has potent activity against gram-positive pathogens. In this study, we confirmed that zabofloxacin showed the most potent in vitro and in vivo activities against drug-resistant Streptococcus pneumoniae. Among the fluoroquinolone compounds, zabofloxacin showed the most [...] Read more.

Zabofloxacin is a novel fluoroquinolone agent that has potent activity against gram-positive pathogens. In this study, we confirmed that zabofloxacin showed the most potent in vitro and in vivo activities against drug-resistant Streptococcus pneumoniae. Among the fluoroquinolone compounds, zabofloxacin showed the most potent in vitro activity against clinical isolates of penicillin-sensitive S. pneumoniae (minimum inhibitory concentration, MIC₉₀: 0.03 mg/L) and penicillin-resistant S. pneumoniae (MIC₉₀: 0.03 mg/L). Against quinolone-resistant S. pneumoniae, zabofloxacin (MIC₉₀: 1 mg/L) was more active than ciprofloxacin, sparfloxacin, and moxifloxacin; however, its activity was the same as that of gemifloxacin. The in vivo activity of zabofloxacin was most potent among the quinolone compounds tested against the systemic infection and respiratory tract infection models in mice. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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11 pages, 1025 KiB

Open AccessArticle

Quantitative Structure Activity Relationship of Cinnamaldehyde Compounds against Wood-Decaying Fungi

by Dongmei Yang

, Hui Wang, Haijian Yuan and Shujun Li^*

Key Laboratory of Bio-Based Material Science and Technology of the Ministry of Education, Northeast Forestry University, Harbin 150040, China

Molecules 2016, 21(11), 1563; https://doi.org/10.3390/molecules21111563 - 17 Nov 2016

Cited by 10 | Viewed by 6217

Abstract

Cinnamaldehyde, of the genius Cinnamomum, is a major constituent of the bark of the cinnamon tree and possesses broad-spectrum antimicrobial activity. In this study, we used best multiple linear regression (BMLR) to develop quantitative structure activity relationship (QSAR) models for cinnamaldehyde derivatives [...] Read more.

Cinnamaldehyde, of the genius Cinnamomum, is a major constituent of the bark of the cinnamon tree and possesses broad-spectrum antimicrobial activity. In this study, we used best multiple linear regression (BMLR) to develop quantitative structure activity relationship (QSAR) models for cinnamaldehyde derivatives against wood-decaying fungi Trametes versicolor and Gloeophyllun trabeum. Based on the two optimal QSAR models, we then designed and synthesized two novel cinnamaldehyde compounds. The QSAR models exhibited good correlation coefficients: R²_Tv = 0.910 for Trametes versicolor and R²_Gt = 0.926 for Gloeophyllun trabeum. Small errors between the experimental and calculated values of two designed compounds indicated that these two QSAR models have strong predictability and stability. Full article

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14 pages, 2192 KiB

Open AccessArticle

Effects of Power Ultrasound on Stability of Cyanidin-3-glucoside Obtained from Blueberry

by Guang-Long Yao, Xing-Hui Ma, Xian-Yin Cao and Jian Chen^*

College of Food Science and Technology, Hainan University, Haikou 570228, China

Molecules 2016, 21(11), 1564; https://doi.org/10.3390/molecules21111564 - 18 Nov 2016

Cited by 15 | Viewed by 6626

Abstract

Power ultrasound (US) could potentially be used in the food industry in the future. However, the extent of anthocyanin degradation by US requires investigation. Cyanidin-3-glucoside (Cy-3-glu) obtained from blueberry extracts was used as research material to investigate the effect of power ultrasound on [...] Read more.

Power ultrasound (US) could potentially be used in the food industry in the future. However, the extent of anthocyanin degradation by US requires investigation. Cyanidin-3-glucoside (Cy-3-glu) obtained from blueberry extracts was used as research material to investigate the effect of power ultrasound on food processing of anthocyanin-rich raw materials. The effects of ultrasonic waves on the stability of Cy-3-glu and on the corresponding changes in UV-Vis spectrum and antioxidant activity were investigated, and the mechanisms of anthocyanin degradation induced by ultrasonic waves were discussed. To explore Cy-3-glu degradation in different environments, we kept the Cy-3-glu solution treated with ultrasonic waves in four concentrations (0%, 10%, 20%, and 50%) of ethanol aqueous solutions to simulate water, beer, wine, and liquor storage environment according to the chemical kinetics method. Results show that the basic spectral characteristics of Cy-3-glu did not significantly change after power ultrasound cell crusher application at 30 °C. However, with anthocyanin degradation, the intensity of the peak for Cy-3-glu at 504 nm significantly decreased (p < 0.05). The degradation kinetics of Cy-3-glu by ultrasonic waves (200–500 W frequency) fitted well to first-order reaction kinetics, and the degradation rate constant of Cy-3-glu under power ultrasound was considerably larger than that under thermal degradation (p < 0.05). The sensitivity of the anthocyanins of blueberry to temperature increased with increasing ethanol concentration, and the longest half-life was observed in 20% ethanol aqueous solution. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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10 pages, 1166 KiB

Open AccessArticle

Circulating IL-27 Is Elevated in Rheumatoid Arthritis Patients

by Xiaofei Lai^1,†, Hongxu Wang^1,†, Ju Cao¹, Ying Li¹, Yubing Dai², Yu Xiang^1,* and Liping Zhang^1,*

¹ Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

² Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1565; https://doi.org/10.3390/molecules21111565 - 18 Nov 2016

Cited by 40 | Viewed by 5804

Abstract

Cytokines are key immunoregulatory molecules that regulate T lymphocyte-mediated immune responses and inflammatory reactions. We determined whether there is aberrant expression of interleukin-27 (IL-27) in rheumatoid arthritis (RA) patients and investigated the clinical significance of these changes. IL-27 is a key cellular factor [...] Read more.

Cytokines are key immunoregulatory molecules that regulate T lymphocyte-mediated immune responses and inflammatory reactions. We determined whether there is aberrant expression of interleukin-27 (IL-27) in rheumatoid arthritis (RA) patients and investigated the clinical significance of these changes. IL-27 is a key cellular factor that regulates the differentiation of CD4+ T cells, which can secrete interleukin-10 (IL-10) and interleukin-17 (IL-17) in vivo. Concentrations of serum IL-27 in 67 RA patients, and 36 sex- and age-matched control subjects were measured by enzyme-linked immunosorbent assay (ELISA). Results showed that concentrations of serum IL-27 in all RA patients were significantly higher than in healthy control subjects, and there was a significant and positive correlation between serum IL-27 levels and disease activity in all RA patients. Levels of serum IL-27 in RA patients were significantly correlated with disease activity score in 28 joints (DAS28). Moreover, immunosuppressive treatment with leflunomide downregulated the levels of IL-27 in active RA patients. Therefore, the elevated production of circulating T cell inflammatory factors contributes to the pathogenesis of RA, and serum IL-27 could potentially serve as a new biomarker of RA disease activity. Full article

(This article belongs to the Special Issue Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday)

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17 pages, 2445 KiB

Open AccessReview

Biophysical Approach to Mechanisms of Cancer Prevention and Treatment with Green Tea Catechins

by Masami Suganuma^1,2,*

, Atsushi Takahashi³, Tatsuro Watanabe⁴, Keisuke Iida^1,2, Takahisa Matsuzaki⁵, Hiroshi Y. Yoshikawa⁵ and Hirota Fujiki⁴

¹ Graduate School of Science and Engineering, Saitama University, Shimo-okubo 255, Sakura-ku, Saitama 338-8570, Japan

² Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Kitaadachi-gun, Saitama 362-0806, Japan

³ Saitama Prefectural Tea Research Institute, Kamiyaganuki 244-2, Iruma, Saitama 358-0042, Japan

⁴ Faculty of Medicine, Saga University, Nabeshima, Saga 849-8501, Japan

⁵ Department of Chemistry, Saitama University, Shimo-okubo 255, Sakura-ku, Saitama 338-8570, Japan

Molecules 2016, 21(11), 1566; https://doi.org/10.3390/molecules21111566 - 18 Nov 2016

Cited by 46 | Viewed by 13017

Abstract

Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on exciting evidence that green tea catechin, (−)-epigallocatechin gallate (EGCG) in drinking water inhibited [...] Read more.

Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on exciting evidence that green tea catechin, (−)-epigallocatechin gallate (EGCG) in drinking water inhibited lung metastasis of B16 melanoma cells, we and other researchers have studied the inhibitory mechanisms of metastasis with green tea catechins using biomechanical tools, atomic force microscopy (AFM) and microfluidic optical stretcher. Specifically, determination of biophysical properties of cancer cells, low cell stiffness, and high deformability in relation to migration, along with biophysical effects, were studied by treatment with green tea catechins. The study with AFM revealed that low average values of Young’s moduli, indicating low cell stiffness, are closely associated with strong potential of cell migration and metastasis for various cancer cells. It is important to note that treatments with EGCG and green tea extract elevated the average values of Young’s moduli resulting in increased stiffness (large elasticity) of melanomas and various cancer cells. We discuss here the biophysical basis of multifunctions of green tea catechins and green tea extract leading to beneficial effects for cancer prevention and treatment. Full article

(This article belongs to the Special Issue Catechins and Human Health: Current State of the Science)

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14 pages, 1430 KiB

Open AccessArticle

Pilot-Scale Production and Thermostability Improvement of the M23 Protease Pseudoalterin from the Deep Sea Bacterium Pseudoalteromonas sp. CF6-2

by Jie Yang^1,2

, Yang Yu^1,2, Bai-Lu Tang^1,2, Shuai Zhong^1,2, Mei Shi^1,2, Bin-Bin Xie^1,2, Xi-Ying Zhang^1,2, Bai-Cheng Zhou², Yu-Zhong Zhang^1,2,3 and Xiu-Lan Chen^1,2,*

¹ State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China

² Marine Biotechnology Research Center, Shandong University, Jinan 250100, China

³ Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266000, China

Molecules 2016, 21(11), 1567; https://doi.org/10.3390/molecules21111567 - 17 Nov 2016

Cited by 5 | Viewed by 4845

Abstract

Pseudoalterin is the most abundant protease secreted by the marine sedimental bacterium Pseudoalteromonas sp. CF6-2 and is a novel cold-adapted metalloprotease of the M23 family. Proteases of the M23 family have high activity towards peptidoglycan and elastin, suggesting their promising biomedical and biotechnological [...] Read more.

Pseudoalterin is the most abundant protease secreted by the marine sedimental bacterium Pseudoalteromonas sp. CF6-2 and is a novel cold-adapted metalloprotease of the M23 family. Proteases of the M23 family have high activity towards peptidoglycan and elastin, suggesting their promising biomedical and biotechnological potentials. To lower the fermentive cost and improve the pseudoalterin production of CF6-2, we optimized the fermentation medium by using single factor experiments, added 0.5% sucrose as a carbon source, and lowered the usage of artery powder from 1.2% to 0.6%. In the optimized medium, pseudoalterin production reached 161.15 ± 3.08 U/mL, 61% greater than that before optimization. We further conducted a small-scale fermentation experiment in a 5-L fermenter and a pilot-scale fermentation experiment in a 50-L fermenter. Pseudoalterin production during pilot-scale fermentation reached 103.48 ± 8.64 U/mL, 77% greater than that before the medium was optimized. In addition, through single factor experiments and orthogonal tests, we developed a compound stabilizer for pseudoalterin, using medically safe sugars and polyols. This stabilizer showed a significant protective effect for pseudoalterin against enzymatic thermal denaturation. These results lay a solid foundation for the industrial production of pseudoalterin and the development of its biomedical and biotechnological potentials. Full article

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13 pages, 1712 KiB

Open AccessArticle

Factors Affecting the Formation of 2:1 Host:Guest Inclusion Complexes of 2-[(R-Phenyl)amine]-1,4-naphthalenediones (PAN) in β- and γ-Cyclodextrins

by Christopher K. Jankowski¹, Christine Lamouroux¹, Manuel Jiménez-Estrada²

, Sebastien Arseneau¹ and Brian D. Wagner^3,*

¹ Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada

² Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, México D.F. 04510, Mexico

³ Department of Chemistry, University of Prince Edward Island, Charlottetown, PEI C1A 4P3, Canada

Molecules 2016, 21(11), 1568; https://doi.org/10.3390/molecules21111568 - 18 Nov 2016

Cited by 8 | Viewed by 8796

Abstract

The molecular hosts cyclodextrins form inclusion complexes with a wide variety of guests, resulting in complexes with various host:guest stoichiometries. In the case of a series of 19 1,4-naphthoquinolines as guests with either β- or γ-cyclodextrin studied using electrospray mass spectroscopy, in most [...] Read more.

The molecular hosts cyclodextrins form inclusion complexes with a wide variety of guests, resulting in complexes with various host:guest stoichiometries. In the case of a series of 19 1,4-naphthoquinolines as guests with either β- or γ-cyclodextrin studied using electrospray mass spectroscopy, in most cases only 1:1 complexes were observed, with 2:1 host:guest complexes observed in just 6 out of 38 host:guest combinations. It is shown that these higher-order complexes were observed only in the case of small (or no) electronically withdrawing substituents, and were much less likely in the case of the larger γ-cyclodextrin host. The size and electronic properties of the substituents involved shows that both steric and electronic factors must be taken into account in predicting which cyclodextrin host:guest stoichiometries will be stable enough to form (or once formed, be robust enough to be observed in the ESI-MS experiments). It is clear that the prediction of host-guest stoichiometry for a specific host-guest pair is complicated, and involves a subtle interplay of both electronic and steric factors. However, there are definite trends, which can be used to help predict host:guest stoichiometry for a given host-guest pair. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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19 pages, 6454 KiB

Open AccessArticle

Ultrasound-Assisted Extraction May Not Be a Better Alternative Approach than Conventional Boiling for Extracting Polysaccharides from Herbal Medicines

by Ka-Man Yip, Jun Xu^*, Wing-Sum Tong, Shan-Shan Zhou, Tao Yi, Zhong-Zhen Zhao and Hu-Biao Chen^*

School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China

Molecules 2016, 21(11), 1569; https://doi.org/10.3390/molecules21111569 - 18 Nov 2016

Cited by 17 | Viewed by 5565

Abstract

In clinical practice polysaccharides from herbal medicines are conventionally prepared by boiling water extraction (BWE), while ultrasound-assisted extraction (UAE) has often been used instead employed in laboratory research due to its strong extraction ability and efficiency. However, if and how the polysaccharides obtained [...] Read more.

In clinical practice polysaccharides from herbal medicines are conventionally prepared by boiling water extraction (BWE), while ultrasound-assisted extraction (UAE) has often been used instead employed in laboratory research due to its strong extraction ability and efficiency. However, if and how the polysaccharides obtained by UAE and BWE are comparable, and hence whether the UAE-based research is instructive for the actual usage of herbal polysaccharides still requires further evaluation. To address this issue, here we chemically analyzed and compared the UAE- and BWE-obtained polysaccharides from three herbal medicines, i.e., Ginseng Radix, Astragali Radix and Dendrobii Officinalis Caulis. Then, the spike recovery of two series of standard dextran and pullulan by UAE and BWE was tested. The results showed that the polysaccharides from the herbal medicines by UAE were quantitatively and qualitatively different with those by BWE. The powerful extraction ability and polysaccharide degradation caused by ultrasound collectively contributed to these differences. It was then revealed that not only the UAE conditions but also the polysaccharide structures could affect the extraction ability and polysaccharide degradation. Given these, we highly recommended that the effects of UAE on polysaccharides from herbal medicines should be first carefully considered before employing it in relevant chemical and pharmacological analysis. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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8 pages, 861 KiB

Open AccessReview

Many Activities, One Structure: Functional Plasticity of Ribozyme Folds

by Matthew W.L. Lau and Adrian R. Ferré-D’Amaré^*

National Heart, Lung and Blood Institute, 50 South Drive, MSC 8012, Bethesda, MD 20892-8012, USA

Molecules 2016, 21(11), 1570; https://doi.org/10.3390/molecules21111570 - 18 Nov 2016

Cited by 18 | Viewed by 6508

Abstract

Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional [...] Read more.

Catalytic RNAs, or ribozymes, are involved in a number of essential biological processes, such as replication of RNA genomes and mobile genetic elements, RNA splicing, translation, and RNA degradation. The function of ribozymes requires the formation of active sites decorated with RNA functional groups within defined three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately determines what 3D structures they adopt (as a function of their environmental conditions). These 3D structures, in turn, give rise to biochemical activity, which can further elaborate them by catalytic rearrangements or association with other molecules. The fitness landscape of a non-periodic linear polymer, such as RNA, relates its primary structure to a phenotype. Two major challenges in the analysis of ribozymes is to map all possible genotypes to their corresponding catalytic activity (that is, to determine their fitness landscape experimentally), and to understand whether their genotypes and three-dimensional structures can support multiple different catalytic functions. Recently, the combined results of experiments that employ in vitro evolution methods, high-throughput sequencing and crystallographic structure determination have hinted at answers to these two questions: while the fitness landscape of ribozymes is rugged, meaning that their catalytic activity cannot be optimized by a smooth trajectory in sequence space, once an RNA achieves a stable three-dimensional fold, it can be endowed with distinctly different biochemical activities through small changes in genotype. This functional plasticity of highly structured RNAs may be particularly advantageous for the adaptation of organisms to drastic changes in selective pressure, or for the development of new biotechnological tools. Full article

(This article belongs to the Special Issue Ribozymes and RNA Catalysis)

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13 pages, 2326 KiB

Open AccessArticle

A Metal-Free Regioselective Multicomponent Approach for the Synthesis of Free Radical Scavenging Pyrimido-Fused Indazoles and Their Fluorescence Studies

by Jeyakannu Palaniraja¹, Selvaraj Mohana Roopan^1,*, G Mokesh Rayalu², Naif Abdullah Al-Dhabi³ and Mariadhas Valan Arasu³

¹ Chemistry of Heterocycles & Natural Product Research Laboratory, Department of Chemistry, School of Advanced Sciences, VIT University, Vellore 632014, Tamilnadu, India

² G Mokesh Rayalu, Department of mathematics, School of Advanced Sciences, VIT University, Vellore 632014, Tamilnadu, India

³ Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

Molecules 2016, 21(11), 1571; https://doi.org/10.3390/molecules21111571 - 18 Nov 2016

Cited by 35 | Viewed by 6161

Abstract

This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b [...] Read more.

This study deals with a new and efficient metal-free regioselective synthesis of pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b]indazole analogues. Response Surface Methodology (RSM) coupled with a Box-Behnken design (BBD) were utilized for exploring the effect of base used (A), temperature of reaction (B) and (C), reaction time. This approach can allow access to a variety of pyrimidoindazole fluorophores and related compounds. The compound N,N-dimethyl-4-(2-phenylpyrimido[1,2-b]indazol-4-yl)aniline (4e) displays the maximum fluorescence intensity at 518 nm and shows a fluorescence quantum yield of 0.068. The synthesized pyramido-fused indazoles have been evaluated for their free radical scavenging activity and compound 4f showed good antioxidant activity. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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12 pages, 1756 KiB

Open AccessArticle

Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors

by Nan Jiang¹

, Yanxin Bu¹, Yu Wang¹, Minhua Nie¹, Dajun Zhang^2,* and Xin Zhai^1,*

¹ Key Lab. of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China

² Department of Chemsitry, Shenyang Medical College, 146 Huanghe North Street, Huanggu District, Shenyang 110034, China

Molecules 2016, 21(11), 1572; https://doi.org/10.3390/molecules21111572 - 18 Nov 2016

Cited by 16 | Viewed by 7089

Abstract

Two novel series of diaryl urea derivatives 5a–i and 13a–l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a–i demonstrated significant activity, and [...] Read more.

Two novel series of diaryl urea derivatives 5a–i and 13a–l were synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives 5a–i demonstrated significant activity, and seven of them are more active than sorafenib, with IC₅₀ values ranging from 0.089 to 5.46 μM. Especially, compound 5a exhibited the most active potency both in cellular (IC₅₀ = 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC₅₀ = 56 nM against EGFR), representing a promising lead for further optimization. Full article

(This article belongs to the Section Medicinal Chemistry)

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44 pages, 13589 KiB

Open AccessReview

Chiral Hypervalent, Pentacoordinated Phosphoranes

by Dorota Krasowska^1,*,†, Jacek Chrzanowski^1,*,†, Piotr Kiełbasiński^1,† and Józef Drabowicz^1,2,*,†

¹ Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland

² Department of Chemistry, Environment Protection and Biotechnology, Jan Dlugosz University in Czestochowa, Armii Krajowej Ave. 13/15, 42-200 Czestochowa, Poland

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1573; https://doi.org/10.3390/molecules21111573 - 21 Nov 2016

Cited by 19 | Viewed by 9348

Abstract

This review presents synthetic procedures applied to the preparation of chiral (mainly optically active) pentacoordinated, hypervalent mono and bicyclic phosphoranes. The mechanisms of their stereoisomerization and their selected interconversions are also presented. Full article

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

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14 pages, 1651 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Benzimidazole Phenylhydrazone Derivatives as Antifungal Agents against Phytopathogenic Fungi

by Xing Wang^1,2,†, Yong-Fei Chen^1,2,†, Wei Yan^1,2, Ling-Ling Cao^1,2 and Yong-Hao Ye^1,2,*

¹ State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China

² Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Nanjing 210095, China

^† These authors contributed equally to this paper.

Molecules 2016, 21(11), 1574; https://doi.org/10.3390/molecules21111574 - 22 Nov 2016

Cited by 42 | Viewed by 11695

Abstract

A series of benzimidazole phenylhydrazone derivatives (6a–6ai) were synthesized and characterized by ¹H-NMR, ESI-MS, and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction as (E)-configuration. All the compounds were screened [...] Read more.

A series of benzimidazole phenylhydrazone derivatives (6a–6ai) were synthesized and characterized by ¹H-NMR, ESI-MS, and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction as (E)-configuration. All the compounds were screened for antifungal activity against Rhizoctonia solani and Magnaporthe oryzae employing a mycelium growth rate method. Compound 6f exhibited significant inhibitory activity against R. solani and M. oryzae with the EC₅₀ values of 1.20 and 1.85 μg/mL, respectively. In vivo testing demonstrated that 6f could effectively control the development of rice sheath blight (RSB) and rice blast (RB) caused by the above two phytopathogens. This work indicated that the compound 6f with a benzimidazole phenylhydrazone scaffold could be considered as a leading structure for the development of novel fungicides. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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14 pages, 3945 KiB

Open AccessArticle

Molecular Docking Optimization in the Context of Multi-Drug Resistant and Sensitive EGFR Mutants

by María Jesús García-Godoy^†, Esteban López-Camacho^†

, José García-Nieto

, Antonio J. Nebro

and José F. Aldana-Montes^*

¹ Khaos Research Group, Departament of Computer Sciences, University of Málaga (UMA), ETSI Informática, Campus de Teatinos, 29071 Málaga, Spain

^† The authors contributed equally to this manuscript.

Molecules 2016, 21(11), 1575; https://doi.org/10.3390/molecules21111575 - 19 Nov 2016

Cited by 18 | Viewed by 7048

Abstract

The human Epidermal Growth Factor (EGFR) plays an important role in signaling pathways, such as cell proliferation and migration. Mutations like G719S, L858R, T790M, G719S/T790M or T790M/L858R can alter its conformation, and, therefore, drug responses from lung cancer patients. In this context, candidate [...] Read more.

The human Epidermal Growth Factor (EGFR) plays an important role in signaling pathways, such as cell proliferation and migration. Mutations like G719S, L858R, T790M, G719S/T790M or T790M/L858R can alter its conformation, and, therefore, drug responses from lung cancer patients. In this context, candidate drugs are being tested and in silico studies are necessary to know how these mutations affect the ligand binding site. This problem can be tackled by using a multi-objective approach applied to the molecular docking problem. According to the literature, few studies are related to the application of multi-objective approaches by minimizing two or more objectives in drug discovery. In this study, we have used four algorithms (NSGA-II, GDE3, SMPSO and MOEA/D) to minimize two objectives: the ligand–receptor intermolecular energy and the RMSD score. We have prepared a set of instances that includes the wild-type EGFR kinase domain and the same receptor with somatic mutations, and then we assessed the performance of the algorithms by applying a quality indicator to evaluate the convergence and diversity of the reference fronts. The MOEA/D algorithm yields the best solutions to these docking problems. The obtained solutions were analyzed, showing promising results to predict candidate EGFR inhibitors by using this multi-objective approach. Full article

(This article belongs to the Collection Molecular Docking)

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15 pages, 1025 KiB

Open AccessFeature PaperArticle

Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile Fraction of a Rosemary (Rosmarinus officinalis L.) Extract

by Pedro Mena¹

, Martina Cirlini¹

, Michele Tassotti¹, Kelli A. Herrlinger², Chiara Dall’Asta¹

and Daniele Del Rio^1,*

¹ Department of Food Science, University of Parma, Parma 43125, Italy

² Kemin Foods, L.C., 2100 Maury Street, Des Moines, IA 50317, USA

Molecules 2016, 21(11), 1576; https://doi.org/10.3390/molecules21111576 - 19 Nov 2016

Cited by 205 | Viewed by 17067

Abstract

This paper presents a comprehensive analysis of the phytochemical profile of a proprietary rosemary (Rosmarinus officinalis L.) extract rich in carnosic acid. A characterization of the (poly)phenolic and volatile fractions of the extract was carried out using mass spectrometric techniques. The (poly)phenolic [...] Read more.

This paper presents a comprehensive analysis of the phytochemical profile of a proprietary rosemary (Rosmarinus officinalis L.) extract rich in carnosic acid. A characterization of the (poly)phenolic and volatile fractions of the extract was carried out using mass spectrometric techniques. The (poly)phenolic composition was assessed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MSⁿ) and a total of 57 compounds were tentatively identified and quantified, 14 of these being detected in rosemary extract for the first time. The rosemary extract contained 24 flavonoids (mainly flavones, although flavonols and flavanones were also detected), 5 phenolic acids, 24 diterpenoids (carnosic acid, carnosol, and rosmanol derivatives), 1 triterpenoid (betulinic acid), and 3 lignans (medioresinol derivatives). Carnosic acid was the predominant phenolic compound. The volatile profile of the rosemary extract was evaluated by head space solid-phase microextraction (HS-SPME) linked to gas chromatography-mass spectrometry (GC-MS). Sixty-three volatile molecules (mainly terpenes, alcohols, esters, aldehydes, and ketones) were identified. This characterization extends the current knowledge on the phytochemistry of Rosmarinus officinalis and is, to our knowledge, the broadest profiling of its secondary metabolites to date. It can assist in the authentication of rosemary extracts or rosemary-containing products or in testing its bioactivity. Moreover, this methodological approach could be applied to the study of other plant-based food ingredients. Full article

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

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25 pages, 2984 KiB

Open AccessFeature PaperReview

Agarose and Its Derivatives as Supports for Enzyme Immobilization

by Paolo Zucca¹

, Roberto Fernandez-Lafuente²

and Enrico Sanjust^1,*

¹ Dipartimento di Scienze Biomediche, Università di Cagliari, 09042 Monserrato (CA), Italy

² Departamento de Biocatalisis, ICP-CSIC; C/Marie Curie 2, Campus UAM-CSIC, Madrid 28049, Spain

Molecules 2016, 21(11), 1577; https://doi.org/10.3390/molecules21111577 - 19 Nov 2016

Cited by 255 | Viewed by 30552

Abstract

Agarose is a polysaccharide obtained from some seaweeds, with a quite particular structure that allows spontaneous gelation. Agarose-based beads are highly porous, mechanically resistant, chemically and physically inert, and sharply hydrophilic. These features—that could be further improved by means of covalent cross-linking—render them [...] Read more.

Agarose is a polysaccharide obtained from some seaweeds, with a quite particular structure that allows spontaneous gelation. Agarose-based beads are highly porous, mechanically resistant, chemically and physically inert, and sharply hydrophilic. These features—that could be further improved by means of covalent cross-linking—render them particularly suitable for enzyme immobilization with a wide range of derivatization methods taking advantage of chemical modification of a fraction of the polymer hydroxyls. The main properties of the polymer are described here, followed by a review of cross-linking and derivatization methods. Some recent, innovative procedures to optimize the catalytic activity and operational stability of the obtained preparations are also described, together with multi-enzyme immobilized systems and the main guidelines to exploit their performances. Full article

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

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9 pages, 1825 KiB

Open AccessCommunication

Direct Separation of Pregabalin Enantiomers Using a Zwitterionic Chiral Selector by High Performance Liquid Chromatography Coupled to Mass Spectrometry and Ultraviolet Detection

by Lakshmi Narayana Chennuru¹, Thirupathi Choppari¹, Ramakrishna Prasad Nandula¹, Tong Zhang² and Pilar Franco^2,*

¹ Daicel Chiral Technologies India, Pvt Ltd, Lab n° 4A, IKP Knowledge Park, Shameerpet, Hyderabad 500078, India

² Chiral Technologies Europe, Parc d’Innovation, Bd. Gonthier d’Andernach, Illkirch F‑67400, France

Molecules 2016, 21(11), 1578; https://doi.org/10.3390/molecules21111578 - 19 Nov 2016

Cited by 15 | Viewed by 7519

Abstract

The chromatographic resolution of pregabalin enantiomers has been often achieved by derivatization of the molecule, in order to reach enough sensitivity at low concentrations of the minor enantiomer present in the active principle. In the present article, the development and optimization of two [...] Read more.

The chromatographic resolution of pregabalin enantiomers has been often achieved by derivatization of the molecule, in order to reach enough sensitivity at low concentrations of the minor enantiomer present in the active principle. In the present article, the development and optimization of two liquid chromatographic methods are presented for the direct resolution of pregabalin enantiomers on a chiral stationary phase (CSP) containing a zwitterionic selector derived from cinchona alkaloid and sulfonic acid (CHIRALPAK ZWIX). The key parameters for the separation as well as the compatibility of chromatographic conditions with different detection modes (ultraviolet and mass spectrometry) were investigated. The resulting methods were found to be selective, of high performance and low limits of detection (2 µg/mL by UV and 1 ng/mL by MS, respectively) and quantification (6 µg/mL by UV and 5 ng/mL by MS, respectively) for the minor enantiomer which is considered as a chiral impurity. Full article

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

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19 pages, 3898 KiB

Open AccessArticle

A Comparative Study of Enantioseparations of N^α-Fmoc Proteinogenic Amino Acids on Quinine-Based Zwitterionic and Anion Exchanger-Type Chiral Stationary Phases under Hydro-Organic Liquid and Subcritical Fluid Chromatographic Conditions

by Gyula Lajkó^1,2, Nóra Grecsó^1,2, Gábor Tóth³, Ferenc Fülöp², Wolfgang Lindner⁴, Antal Péter¹ and István Ilisz^1,*

¹ Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary

² Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary

³ Institute of Medical Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary

⁴ Department of Analytical Chemistry, University of Vienna, Währinger Strasse 38, 1090 Vienna, Austria

Molecules 2016, 21(11), 1579; https://doi.org/10.3390/molecules21111579 - 22 Nov 2016

Cited by 12 | Viewed by 7359

Abstract

The focus of this contribution is a comparative investigation of enantioseparations of 19 N^α-Fmoc proteinogenic amino acids on Quinine-based zwitterionic and anion-exchanger type chiral stationary phases employing hydro-organic and polar-ionic liquid and subcritical fluid chromatographic conditions. Effects of mobile phase [...] Read more.

The focus of this contribution is a comparative investigation of enantioseparations of 19 N^α-Fmoc proteinogenic amino acids on Quinine-based zwitterionic and anion-exchanger type chiral stationary phases employing hydro-organic and polar-ionic liquid and subcritical fluid chromatographic conditions. Effects of mobile phase composition (including additives, e.g., water, basis and acids) and nature of chiral selectors on the chromatographic performances were studied at different chromatographic modes. Thermodynamic parameters of the temperature dependent enantioseparation results were calculated in the temperature range 5–50 °C applying plots of lnα versus 1/T. The differences in standard enthalpy and standard entropy for a given pair of enantiomers were calculated and served as a basis for comparisons. Elution sequence in all cases was determined, where a general rule could be observed, both in liquid and subcritical fluid chromatographic mode the d-enantiomers eluted before the L ones. In both modes, the principles of ion exchange chromatography apply. Full article

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

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31 pages, 2148 KiB

Open AccessReview

A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering

by Pariksha J. Kondiah, Yahya E. Choonara

, Pierre P. D. Kondiah, Thashree Marimuthu

, Pradeep Kumar

, Lisa C. Du Toit and Viness Pillay^*

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa

Molecules 2016, 21(11), 1580; https://doi.org/10.3390/molecules21111580 - 21 Nov 2016

Cited by 178 | Viewed by 15637

Abstract

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive [...] Read more.

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties. Full article

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

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10 pages, 1080 KiB

Open AccessArticle

Semisynthetic and SAR Studies of Amide Derivatives of Neocrotocembraneic Acid as Potential Antitumor Agents

by Hai Shang¹, Ling-Yu Li¹

, Wei-Hua Cheng¹, Jun Luo^1,2, Hong-Wu Zhang¹ and Zhong-Mei Zou^1,*

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

² School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, China

Molecules 2016, 21(11), 1581; https://doi.org/10.3390/molecules21111581 - 19 Nov 2016

Cited by 1 | Viewed by 4093

Abstract

A series of novel amide derivatives of cembranoid neocrotocembraneic acid were designed and synthesized. The antiproliferative activities of these derivatives were evaluated against three human tumor cell lines (the human cervical cancer cell line HeLa, chronic myeloid leukemia cell line K562 and leukemia [...] Read more.

A series of novel amide derivatives of cembranoid neocrotocembraneic acid were designed and synthesized. The antiproliferative activities of these derivatives were evaluated against three human tumor cell lines (the human cervical cancer cell line HeLa, chronic myeloid leukemia cell line K562 and leukemia multidrug-resistant cell line K562/A02). Some of the synthesized compounds exhibited moderate to good activity against all three cancer cell lines. Particularly, compound 8a exhibited more potent antiproliferative activity than the reference drug etoposide against drug-resistant cell line K562/A02, indicating that it possessed a great potential for further development as a multidrug resistance modulator by structural modification. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 931 KiB

Open AccessArticle

Synthesis of a Morpholino Nucleic Acid (MNA)-Uridine Phosphoramidite, and Exon Skipping Using MNA/2′-O-Methyl Mixmer Antisense Oligonucleotide

by Suxiang Chen^1,2, Bao T. Le^1,2, Kamal Rahimizadeh¹, Khalil Shaikh³, Narinder Mohal³ and Rakesh N. Veedu^1,2,*

¹ Centre for Comparative Genomics, Murdoch University, Perth 6150, Australia

² Western Australian Neuroscience Research Institute, Perth 6150, Australia

³ GMK Research Laboratories Pvt. Ltd., Mallapur, Hyderabad 500 076, India

Molecules 2016, 21(11), 1582; https://doi.org/10.3390/molecules21111582 - 22 Nov 2016

Cited by 24 | Viewed by 8525

Abstract

In this study, we synthesised a morpholino nucleoside-uridine (MNA-U) phosphoramidite and evaluated the potential of a MNA-modified antisense oligonucleotide (AO) sequences to induce exon 23 skipping in mdx mouse myotubes in vitro towards extending the applicability of morpholino chemistry with other nucleotide monomers. [...] Read more.

In this study, we synthesised a morpholino nucleoside-uridine (MNA-U) phosphoramidite and evaluated the potential of a MNA-modified antisense oligonucleotide (AO) sequences to induce exon 23 skipping in mdx mouse myotubes in vitro towards extending the applicability of morpholino chemistry with other nucleotide monomers. We designed, synthesised, and compared exon skipping efficiencies of 20 mer MNA-modified 2′-O-methyl RNA mixmer AO on a phosphorothioate backbone (MNA/2′-OMePS) to the corresponding fully modified 2′-O-methyl RNA AO (2′-OMePS) as a control. Our results showed that the MNA/2′-OMePS efficiently induced exon 23 skipping. As expected, the 2′-OMePS AO control yielded efficient exon 23 skipping. Under the applied conditions, both the AOs showed minor products corresponding to exon 22/23 dual exon skipping in low yield. As these are very preliminary data, more detailed studies are necessary; however, based on the preliminary results, MNA nucleotides might be useful in constructing antisense oligonucleotides. Full article

(This article belongs to the Special Issue Nucleic Acid-based Drug)

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14 pages, 3661 KiB

Open AccessArticle

Temperature-Triggered Switchable Helix-Helix Inversion of Poly(phenylacetylene) Bearing l-Valine Ethyl Ester Pendants and Its Chiral Recognition Ability

by Yanli Zhou¹, Chunhong Zhang^1,*

, Yuan Qiu¹, Lijia Liu^1,*

, Taotao Yang¹, Hongxing Dong¹, Toshifumi Satoh²

and Yoshio Okamoto^1,3

¹ Polymer Materials Research Center, Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, China

² Faculty of Engineering, Hokkaido University, Sapporo 060-8628, Japan

³ Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan

Molecules 2016, 21(11), 1583; https://doi.org/10.3390/molecules21111583 - 21 Nov 2016

Cited by 22 | Viewed by 6253

Abstract

A phenylacetylene containing the l-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh₄) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not [...] Read more.

A phenylacetylene containing the l-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh₄) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not observed in highly polar solvents, such as N,N′-dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the sign of the CD absorption became reversed, but recovered after cooling the solution to room temperature. Even after six cycles of the heating-cooling treatment, the helix sense of the PPAA-Val’s backbone was still switchable without loss of the CD intensity. The PPAA-Val was then coated on silica gel particles to produce novel chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). These novel PPAA-Val based CSPs showed a high chiral recognition ability for racemic mandelonitrile (α = 2.18) and racemic trans-N,N′-diphenylcyclohexane-1,2-dicarboxamide (α = 2.60). Additionally, the one-handed helical cis-polyene backbone of PPAA-Val was irreversibly destroyed to afford PPAA-Val-H by heating in dimethyl sulfoxide (DMSO) accompanied by the complete disappearance of the Cotton effect. Although PPAA-Val-H had the same l-valine ethyl ester pendants as its cis-isomer PPAA-Val, it showed no chiral recognition. It was concluded that the one-handed helical cis-polyene backbone of PPAA-Val plays an important role in the chiral recognition ability. Full article

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

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13 pages, 3540 KiB

Open AccessArticle

Ultrasound-Assisted Extraction, Centrifugation and Ultrafiltration: Multistage Process for Polyphenol Recovery from Purple Sweet Potatoes

by Zhenzhou Zhu¹, Tian Jiang¹

, Jingren He^1,*, Francisco J. Barba^2,*

, Giancarlo Cravotto³

and Mohamed Koubaa⁴

¹ College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China

² Nutrition and Food Science Area, Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine Department, Faculty of Pharmacy, Universitat de València, Avda. Vicent Andrés Estellés, s/n, 46100 Burjassot, València, Spain

³ Dipartimento di Scienza e Tecnologia del Farmaco, University of Turin, Via P. Giuria 9, 10125 Turin, Italy

⁴ Centre de Recherche de Royallieu, Laboratoire Transformations Intégrées de la Matière Renouvelable (UTC/ESCOM, EA 4297 TIMR), Université de Technologie de Compiègne, CS 60319, 60203 Compiègne CEDEX, France

Molecules 2016, 21(11), 1584; https://doi.org/10.3390/molecules21111584 - 20 Nov 2016

Cited by 32 | Viewed by 9025

Abstract

This work provides an evaluation of an ultrasound-assisted, combined extraction, centrifugation and ultrafiltration process for the optimal recovery of polyphenols. A purple sweet potato (PSP) extract has been obtained using ultrasonic circulating extraction equipment at a power of 840 W, a frequency of [...] Read more.

This work provides an evaluation of an ultrasound-assisted, combined extraction, centrifugation and ultrafiltration process for the optimal recovery of polyphenols. A purple sweet potato (PSP) extract has been obtained using ultrasonic circulating extraction equipment at a power of 840 W, a frequency of 59 kHz and using water as solvent. Extract ultrafiltration, using polyethersulfone (PES), was carried out for the recovery of polyphenol, protein and anthocyanin. Pre-treatment, via the centrifugation of purple sweet potato extract at 2500 rpm over 6 min, led to better polyphenol recovery, with satisfactory protein removal (reused for future purposes), than PSP extract filtration without centrifugation. Results showed that anthocyanin was efficiently recovered (99%) from permeate. The exponential model fit well with the experimental ultrafiltration data and led to the calculation of the membrane’s fouling coefficient. The optimization of centrifugation conditions showed that, at a centrifugation speed of 4000 rpm (1195× g) and duration of 7.74 min, the optimized polyphenol recovery and fouling coefficient were 34.5% and 29.5 m⁻¹, respectively. The removal of proteins in the centrifugation process means that most of the anthocyanin content (90%) remained after filtration. No significant differences in the intensities of the HPLC-DAD-ESI-MS² peaks were found in the samples taken before and after centrifugation for the main anthocyanins; peonidin-3-feruloylsophoroside-5-glucoside, peonidin-3-caffeoyl-p-hydroxybenzoylsophoroside-5-glucoside, and peonidin-3-caffeoyl-feruloyl sophoroside-5-glucoside. This proves that centrifugation is an efficient method for protein removal without anthocyanin loss. This study considers this process an ultrasound-assisted extraction-centrifugation-ultrafiltration for purple sweet potato valorization in “green” technology. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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29 pages, 6261 KiB

Open AccessReview

Carbon-Based Materials for Photo-Triggered Theranostic Applications

by Karunya Albert¹

and Hsin-Yun Hsu^1,2,*

¹ Institute of Molecular Science, National Chiao-Tung University, Hsinchu 30010, Taiwan

² Department of Applied Chemistry, National Chiao-Tung University, Hsinchu 30010, Taiwan

Molecules 2016, 21(11), 1585; https://doi.org/10.3390/molecules21111585 - 20 Nov 2016

Cited by 61 | Viewed by 10776

Abstract

Carbon-based nanomaterials serve as a type of smart material for photo-triggered disease theranostics. The inherent physicochemical properties of these nanomaterials facilitate their use for less invasive treatments. This review summarizes the properties and applications of materials including fullerene, nanotubes, nanohorns, nanodots and nanographenes [...] Read more.

Carbon-based nanomaterials serve as a type of smart material for photo-triggered disease theranostics. The inherent physicochemical properties of these nanomaterials facilitate their use for less invasive treatments. This review summarizes the properties and applications of materials including fullerene, nanotubes, nanohorns, nanodots and nanographenes for photodynamic nanomedicine in cancer and antimicrobial therapies. Carbon nanomaterials themselves do not usually act as photodynamic therapy (PDT) agents owing to the high hydrophobicity, however, when the surface is passivated or functionalized, these materials become great vehicles for PDT. Moreover, conjugation of carbonaceous nanomaterials with the photosensitizer (PS) and relevant targeting ligands enhances properties such as selectivity, stability, and high quantum yield, making them readily available for versatile biomedical applications. Full article

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

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15 pages, 2038 KiB

Open AccessArticle

Bio-Guided Isolation of Methanol-Soluble Metabolites of Common Spruce (Picea abies) Bark by-Products and Investigation of Their Dermo-Cosmetic Properties

by Apostolis Angelis^1,2,*, Jane Hubert^1,*, Nektarios Aligiannis²

, Rozalia Michalea², Amin Abedini¹, Jean-Marc Nuzillard¹

, Sophie C. Gangloff³

, Alexios-Leandros Skaltsounis² and Jean-Hugues Renault¹

¹ Institut de Chimie Moléculaire de Reims, UMR CNRS 7312, SFR CAP’SANTE, UFR de Pharmacie, Université de Reims Champagne-Ardenne, Reims 51687, France

² Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Panepistimioupolis, Zografou, Athens 15771, Greece

³ Biomatériaux et Inflammation en Site Osseux, EA 4691, SFR CAP-Santé, UFR de Pharmacie, Université de Reims Champagne Ardenne, Reims 51100, France

Molecules 2016, 21(11), 1586; https://doi.org/10.3390/molecules21111586 - 21 Nov 2016

Cited by 37 | Viewed by 7353

Abstract

Common spruce (Picea abies L.) is a fast-growing coniferous tree, widely used in several countries for the production of sawn wood, timber and pulp. During this industrial exploitation, large quantities of barks are generated as waste materials. The aim of this study [...] Read more.

Common spruce (Picea abies L.) is a fast-growing coniferous tree, widely used in several countries for the production of sawn wood, timber and pulp. During this industrial exploitation, large quantities of barks are generated as waste materials. The aim of this study was the bio-guided investigation and the effective recovery of methanol-soluble metabolites of common spruce bark for the development of new dermo-cosmetic agents. The active methanol extract was initially fractionated by Centrifugal Partition Chromatography (CPC) using a triphasic solvent system in a step-gradient elution mode. All resulting fractions were evaluated for their antibacterial activity, antioxidant activity and their capability to inhibit tyrosinase, elastase and collagenase activity. In parallel, the chemical composition of each fraction was established by combining a ¹³C-NMR dereplication approach and 2D-NMR analyses. As a result, fourteen secondary metabolites corresponding to stilbene, flavonoid and phenolic acid derivatives were directly identified in the CPC fractions. A high amount (0.93 g) of E-astringin was recovered from 3 g of crude extract in a single 125 min run. E-Astringin significantly induced the tyrosinase activity while E-piceid, taxifolin, and taxifolin-3′-O-glucopyranoside exhibited significant anti-tyrosinase activity. The above compounds showed important anti-collagenase and antimicrobial activities, thus providing new perspectives for potential applications as cosmetic ingredients. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 672 KiB

Open AccessArticle

Structural Investigation of Cell Wall Xylan Polysaccharides from the Leaves of Algerian Argania spinosa

by Kadda Hachem^1,2,*

, Céline Faugeron³, Meriem Kaid-Harche² and Vincent Gloaguen³

¹ Laboratoire de Biotoxicologie, Pharmacognosie et Valorisation Biologique des Plantes (LBPVBP), Département de biologie, Faculté des sciences, Université Dr. Tahar Moulay de Saida, BP 138 cité ENNASR, 20000 Saida, Algérie

² Laboratoire des Productions, Valorisations Végétales et Microbiennes (LP2VM), Département de Biotechnologie, Faculté des sciences de la nature et de la vie, Université des Sciences et de la Technologie d’Oran, BP 1505 El M’Naouar, 31000 Oran, Algérie

³ Laboratoire de Chimie des Substances Naturelles (EA1069), Faculté des Sciences et Techniques, Université de Limoges, 123 avenue Albert Thomas, 87060 Limoges, France

Molecules 2016, 21(11), 1587; https://doi.org/10.3390/molecules21111587 - 21 Nov 2016

Cited by 16 | Viewed by 6042

Abstract

Xylan-type polysaccharides were isolated from the leaves of Argania spinosa (L.) Skeels collected in the Tindouf area (southwestern Algeria). Xylan fractions were obtained by sequential alkaline extractions and purified on Sepharose CL-4B. The xylan structure was investigated by enzymatic hydrolysis with an endo-β(1→4)-xylanase [...] Read more.

Xylan-type polysaccharides were isolated from the leaves of Argania spinosa (L.) Skeels collected in the Tindouf area (southwestern Algeria). Xylan fractions were obtained by sequential alkaline extractions and purified on Sepharose CL-4B. The xylan structure was investigated by enzymatic hydrolysis with an endo-β(1→4)-xylanase followed by chromatography of the resulting fragments on Biogel P2, characterization by sugar analysis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS ). The results show that the A. spinosa xylan is composed of a β-(1→4)-d-xylopyranose backbone substituted with 4-O-methyl-d-glucuronic acid and L-arabinose residues. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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13 pages, 3993 KiB

Open AccessReview

Structures and Ribosomal Interaction of Ribosome-Inactivating Proteins

by Wei-Wei Shi, Amanda Nga-Sze Mak, Kam-Bo Wong and Pang-Chui Shaw^*

Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

Molecules 2016, 21(11), 1588; https://doi.org/10.3390/molecules21111588 - 21 Nov 2016

Cited by 42 | Viewed by 9002

Abstract

Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA N-glycosidases that depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. RIPs are grouped into three types according to the [...] Read more.

Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA N-glycosidases that depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. RIPs are grouped into three types according to the number of subunits and the organization of the precursor sequences. RIPs are two-domain proteins, with the active site located in the cleft between the N- and C-terminal domains. It has been found that the basic surface residues of the RIPs promote rapid and specific targeting to the ribosome and a number of RIPs have been shown to interact with the C-terminal regions of the P proteins of the ribosome. At present, the structural basis for the interaction of trichosanthin and ricin-A chain toward P2 peptide is known. This review surveys the structural features of the representative RIPs and discusses how they approach and interact with the ribosome. Full article

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

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12 pages, 558 KiB

Open AccessArticle

New Homoisoflavanes, a New Alkaloid and Spirostane Steroids from the Roots of Herreria montevidensis Klotzsch ex Griseb. (Herreriaceae)

by María Dutra-Behrens¹ and Guillermo Schmeda-Hirschmann^2,*

¹ Departamento de Produtos Naturais, Instituto de Tecnologia em Fármacos da Fundação Oswaldo Cruz–Farmanguinhos/Fiocruz, Rua Sizenando Nabuco 100, 21041-250 Rio de Janeiro, Brazil

² Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, 3460000 Talca, Chile

Molecules 2016, 21(11), 1589; https://doi.org/10.3390/molecules21111589 - 21 Nov 2016

Cited by 5 | Viewed by 4616

Abstract

The roots of the South American vine Herreria montevidensis Klotzsch ex Griseb. (Herreriaceae) are used in traditional medicine by several Amerindian groups of the Paraguayan Chaco. Little is known on the chemistry of the plant, despite its widespread use across the South American [...] Read more.

The roots of the South American vine Herreria montevidensis Klotzsch ex Griseb. (Herreriaceae) are used in traditional medicine by several Amerindian groups of the Paraguayan Chaco. Little is known on the chemistry of the plant, despite its widespread use across the South American Chaco. From the ethyl acetate/methanol 1:1 extract of the roots, four new and one known homoisoflavanoid, two flavan derivatives, a stilbene, a new alkaloid, and three new and four known spirostane steroids were isolated. The corresponding structures were elucidated by spectroscopic and spectrometric means. The homoisoflavonoids of the plant are related to compounds isolated from the Dracaenaceae (formerly Agavaceae) sources of the Chinese crude drug Dragon’s Blood. The new alkaloid is a novel skeleton that can be used as a chemical marker of Herreria. The spirostane steroids suggest chemotaxonomic relations with the Liliales. This is the first comprehensive report on the chemistry of a South American Herreria species. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1148 KiB

Open AccessArticle

Structural Analysis of Sortase A Inhibitors

by Georgiana Nitulescu

, Anca Zanfirescu, Octavian Tudorel Olaru

, Isabela Madalina Nicorescu, George Mihai Nitulescu^*

and Denisa Margina

Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, Bucharest 020956, Romania

Molecules 2016, 21(11), 1591; https://doi.org/10.3390/molecules21111591 - 22 Nov 2016

Cited by 24 | Viewed by 7092

Abstract

Bacterial sortases are cysteine transpeptidases that regulate the covalent linkage of several surface protein virulence factors in Gram-positive bacteria. Virulence factors play significant roles in adhesion, invasion of host tissues, biofilm formation and immune evasion, mediating the bacterial pathogenesis and infectivity. Therefore, sortases [...] Read more.

Bacterial sortases are cysteine transpeptidases that regulate the covalent linkage of several surface protein virulence factors in Gram-positive bacteria. Virulence factors play significant roles in adhesion, invasion of host tissues, biofilm formation and immune evasion, mediating the bacterial pathogenesis and infectivity. Therefore, sortases are emerging as important targets for the design of new anti-infective agents. We employed a computational study, based on structure derived descriptors and molecular fingerprints, in order to develop simple classification methods which could allow predicting low active or high active SrtA inhibitors. Our results indicate that a highly active SrtA inhibitor has a molecular weight ranging between 180 and 600, contains one up to four nitrogen atoms, up to three oxygen atoms and under 18 hydrogen atoms. Also the hydrogen acceptor number and the molecular flexibility, as assessed by the number of rotatable bounds, have emerged as the most relevant descriptors for SrtA affinity. The Bemis-Murcko scaffolding revealed favoured scaffolds as containing at least two ring structures bonded directly or merged in a condensed cycle. This data represent a valuable tool for identifying new potent SrtA inhibitors, potential anti-virulence agents targeted against Gram-positive bacteria, including multiresistant strains. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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12 pages, 701 KiB

Open AccessArticle

Synthesis and Antifungal Screening of 2-{[1-(5-Alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones

by Veronika Opletalova¹

, Jan Dolezel², Jiri Kunes³, Vladimir Buchta^4,5, Marcela Vejsova^4,5 and Marta Kucerova-Chlupacova^1,*

¹ Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

² GlaxoSmithKline, Hvezdova 1734/2c, 140 00 Prague, Czech Republic

³ Department of Inorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

⁴ Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

⁵ Department of Clinical Microbiology, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic

Molecules 2016, 21(11), 1592; https://doi.org/10.3390/molecules21111592 - 23 Nov 2016

Cited by 9 | Viewed by 6759

Abstract

Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against a panel of eight fungal strains–Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton [...] Read more.

Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against a panel of eight fungal strains–Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton interdigitale 445. 1,3-Thiazolidin-4-ones exhibited activity against all strains, the most potent derivative was 2-{[1-(5-butylpyrazin-2-yl)ethylidene]hydrazono}e-1,3-thiazolidin-4-one. Susceptibility of C. glabrata to the studied 1,3-thiazolidin-4-ones (minimum inhibitory concentrations (MICs) were in the range 0.57 to 2.78 mg/L) is of great interest as this opportunistic pathogen is poorly susceptible to azoles and becomes resistant to echinocandins. Antifungal potency of thiosemicarbazones was slightly lower than that of 1,3-thiazolidin-4-ones. Full article

(This article belongs to the Special Issue Selected Papers from the 8th Central European Conference ‘Chemistry towards Biology’ (CTB-2016))

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17 pages, 2808 KiB

Open AccessArticle

Stereoselective Alkane Oxidation with meta-Chloroperoxybenzoic Acid (MCPBA) Catalyzed by Organometallic Cobalt Complexes

by Georgiy B. Shul’pin^1,2,*, Dmitriy A. Loginov³, Lidia S. Shul’pina³

, Nikolay S. Ikonnikov³, Vladislav O. Idrisov³, Mikhail M. Vinogradov³, Sergey N. Osipov³, Yulia V. Nelyubina³ and Polina M. Tyubaeva²

¹ Semenov Institute of Chemical Physics, Russian Academy of Sciences, ulitsa Kosygina, dom 4, Moscow 119991, Russia

² Chair of Chemistry and Physics, Plekhanov Russian University of Economics, Stremyannyi pereulok, dom 36, Moscow 117997, Russia

³ Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ulitsaVavilova, dom 28, Moscow 119991, Russia

Molecules 2016, 21(11), 1593; https://doi.org/10.3390/molecules21111593 - 22 Nov 2016

Cited by 29 | Viewed by 10744

Abstract

Cobalt pi-complexes, previously described in the literature and specially synthesized and characterized in this work, were used as catalysts in homogeneous oxidation of organic compounds with peroxides. These complexes contain pi-butadienyl and pi-cyclopentadienyl ligands: [(tetramethylcyclobutadiene)(benzene)cobalt] hexafluorophosphate, [(C₄Me₄)Co(C₆H [...] Read more.

Cobalt pi-complexes, previously described in the literature and specially synthesized and characterized in this work, were used as catalysts in homogeneous oxidation of organic compounds with peroxides. These complexes contain pi-butadienyl and pi-cyclopentadienyl ligands: [(tetramethylcyclobutadiene)(benzene)cobalt] hexafluorophosphate, [(C₄Me₄)Co(C₆H₆)]PF₆ (1); diiodo(carbonyl)(pentamethylcyclopentadienyl)cobalt, Cp*Co(CO)I₂ (2); diiodo(carbonyl)(cyclopentadienyl)cobalt, CpCo(CO)I₂ (3); (tetramethylcyclobutadiene)(dicarbonyl)(iodo)cobalt, (C₄Me₄)Co(CO)₂I (4); [(tetramethylcyclobutadiene)(acetonitrile)(2,2′-bipyridyl)cobalt] hexafluorophosphate, [(C₄Me₄)Co(bipy)(MeCN)]PF₆ (5); bis[dicarbonyl(B-cyclohexylborole)]cobalt, [(C₄H₄BCy)Co(CO)₂]₂ (6); [(pentamethylcyclopentadienyl)(iodo)(1,10-phenanthroline)cobalt] hexafluorophosphate, [Cp*Co(phen)I]PF₆ (7); diiodo(cyclopentadienyl)cobalt, [CpCoI₂]₂ (8); [(cyclopentadienyl)(iodo)(2,2′-bipyridyl)cobalt] hexafluorophosphate, [CpCo(bipy)I]PF₆ (9); and [(pentamethylcyclopentadienyl)(iodo)(2,2′-bipyridyl)cobalt] hexafluorophosphate, [Cp*Co(bipy)I]PF₆ (10). Complexes 1 and 2 catalyze very efficient and stereoselective oxygenation of tertiary C–H bonds in isomeric dimethylcyclohexanes with MCBA: cyclohexanols are produced in 39 and 53% yields and with the trans/cis ratio (of isomers with mutual trans- or cis-configuration of two methyl groups) 0.05 and 0.06, respectively. Addition of nitric acid as co-catalyst dramatically enhances both the yield of oxygenates and stereoselectivity parameter. In contrast to compounds 1 and 2, complexes 9 and 10 turned out to be very poor catalysts (the yields of oxygenates in the reaction with cis-1,2-dimethylcyclohexane were only 5%–7% and trans/cis ratio 0.8 indicated that the oxidation is not stereoselective). The chromatograms of the reaction mixture obtained before and after reduction with PPh₃ are very similar, which testifies that alkyl hydroperoxides are not formed in this oxidation. It can be thus concluded that the interaction of the alkanes with MCPBA occurs without the formation of free radicals. The complexes catalyze oxidation of alcohols with tert-butylhydroperoxide (TBHP). For example, tert-BuOOH efficiently oxidizes 1-phenylethanol to acetophenone in 98% yield if compound 1 is used as a catalyst. Full article

(This article belongs to the Special Issue Reactions of Hydrocarbons and other C‒H Compounds)

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19 pages, 8019 KiB

Open AccessArticle

Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

by Giorgia Adamo¹, Natascia Grimaldi², Simona Campora¹

, Donatella Bulone³

, Maria Luisa Bondì⁴, Mohamad Al-Sheikhly⁵, Maria Antonietta Sabatino², Clelia Dispenza² and Giulio Ghersi^1,*

¹ Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy

² Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 6, 90128 Palermo, Italy

³ Consiglio Nazionale delle Ricerche (CNR)—Istituto di Biofisica (IBF) UOS Palermo, Via U. La Malfa 153, 90146 Palermo, Italy

⁴ Consiglio Nazionale delle Ricerche (CNR)—Istituto per lo Studio dei Materiali Nanostrutturati (ISMN) UOS Palermo, Via Ugo La Malfa, 153, 90146 Palermo, Italy

⁵ Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742, USA

Molecules 2016, 21(11), 1594; https://doi.org/10.3390/molecules21111594 - 23 Nov 2016

Cited by 36 | Viewed by 8340

Abstract

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) [...] Read more.

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy. Full article

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

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19 pages, 2872 KiB

Open AccessArticle

New Thiazolyl-triazole Schiff Bases: Synthesis and Evaluation of the Anti-Candida Potential

by Anca Stana¹

, Alexandra Enache¹, Dan Cristian Vodnar²

, Cristina Nastasă^1,*, Daniela Benedec³, Ioana Ionuț¹, Cezar Login⁴

, Gabriel Marc¹

, Ovidiu Oniga¹ and Brîndușa Tiperciuc¹

¹ Department of Pharmaceutical Chemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania

² Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 3-5 Mănăștur Street, RO-400372 Cluj-Napoca, Romania

³ Department of Pharmacognosy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 12 Ion Creangă Street, RO-400010 Cluj-Napoca, Romania

⁴ Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 1 Clinicilor Street, RO-400006 Cluj-Napoca, Romania

Molecules 2016, 21(11), 1595; https://doi.org/10.3390/molecules21111595 - 22 Nov 2016

Cited by 34 | Viewed by 7906

Abstract

In the context of the dangerous phenomenon of fungal resistance to the available therapies, we present here the chemical synthesis of a new series of thiazolyl-triazole Schiff bases B1–B15, which were in vitro assessed for their anti-Candida potential. Compound [...] Read more.

In the context of the dangerous phenomenon of fungal resistance to the available therapies, we present here the chemical synthesis of a new series of thiazolyl-triazole Schiff bases B1–B15, which were in vitro assessed for their anti-Candida potential. Compound B10 was found to be more potent against Candida spp. when compared with the reference drugs Fluconazole and Ketoconazole. A docking study of the newly synthesized Schiff bases was performed, and results showed good binding affinity in the active site of co-crystallized Itraconazole-lanosterol 14α-demethylase isolated from Saccharomyces cerevisiae. An in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) study was done in order to predict some pharmacokinetic and pharmacotoxicological properties. The Schiff bases showed good drug-like properties. The results of in vitro anti-Candida activity, a docking study and ADMET prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, B10, which can be further optimized as a lead compound. Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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12 pages, 980 KiB

Open AccessReview

4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on Insulin Resistance Associated with Obesity

by Anaguiven Avalos-Soriano¹

, Ricardo De la Cruz-Cordero², Jorge L. Rosado¹ and Teresa Garcia-Gasca^1,*

¹ Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Juriquilla, Querétaro, Qro. 76230, Mexico

² Nucitec S.A. de C.V. Querétaro, Qro. 76215, Mexico

Molecules 2016, 21(11), 1596; https://doi.org/10.3390/molecules21111596 - 22 Nov 2016

Cited by 70 | Viewed by 14924

Abstract

Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic [...] Read more.

Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models. Full article

(This article belongs to the Special Issue Natural Products in Anti-Obesity Therapy)

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14 pages, 2433 KiB

Open AccessArticle

Kuwanon G Preserves LPS-Induced Disruption of Gut Epithelial Barrier In Vitro

by Hengli Guo¹, Youhua Xu^1,2,*, Wei Huang^1,2,3, Hua Zhou^1,2,4

, Zhaoguang Zheng⁵, Yonghua Zhao^1,2, Bao He⁵, Tingting Zhu^1,2,3, Shanshan Tang¹ and Quan Zhu^1,2,5

¹ Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China

² State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China

³ Affiliated Hospital of Southwest Medical University, Luzhou 640000, China

⁴ Macau Institute for Applied Research in Medicine and Health, Avenida Wai Long, Taipa, Macao, China

⁵ Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou 510760, China

Molecules 2016, 21(11), 1597; https://doi.org/10.3390/molecules21111597 - 22 Nov 2016

Cited by 38 | Viewed by 8845

Abstract

Defects in the gut epithelial barrier have now been recognized to be responsible for diabetic endotoxemia. In everyday life, Mulberry leaf tea is widely used in Asian nations due to its proposed benefits to health and control of diabetes. Evidence indicates the potential [...] Read more.

Defects in the gut epithelial barrier have now been recognized to be responsible for diabetic endotoxemia. In everyday life, Mulberry leaf tea is widely used in Asian nations due to its proposed benefits to health and control of diabetes. Evidence indicates the potential role of Kuwanon G (KWG), a component from Morus alba L., on blocking the gut epithelial barrier. In lipopolysaccharides (LPS)-damaged Caco-2 cells, it was found that KWG increased the viability of cells in a concentration-dependent manner. KWG administration significantly elevated the anti-oxidant abilities via increasing ratio of superoxidase dismutase (SOD)/malondialdehyde (MDA) and decreasing reactive oxygen species (ROS) within the cells. During KWG incubation, pro-inflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly reduced, tight junction proteins including zonula occludens (ZO)-1, intercellular adhesion molecule (ICAM)-1 and Occludin were dramatically increased as detected by immunofluorescence assay, trans-epithelial electrical resistance was significantly increased and the transmission of albumin-fluorescein isothiocyanate (FITC) across the barrier was decreased. In conclusion, the present study demonstrated that KWG could ameliorate LPS-induced disruption of the gut epithelial barrier by increasing cell viability and tight junction between cells, and decreasing pro-inflammatory cytokines and oxidative damage. Full article

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

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18 pages, 2414 KiB

Open AccessArticle

Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

by Mehlika Dilek Altıntop^1,*, Halide Edip Temel², Belgin Sever¹

, Gülşen Akalın Çiftçi²

and Zafer Asım Kaplancıklı¹

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

² Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

Molecules 2016, 21(11), 1598; https://doi.org/10.3390/molecules21111598 - 22 Nov 2016

Cited by 30 | Viewed by 6653

Abstract

New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their [...] Read more.

New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1′-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound 5 did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound 5 and cholinesterases. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 6395 KiB

Open AccessArticle

Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the Proliferation and Induced Apoptosis of Activated HSC-T6 Cells

by Siling Bi^1,†, Fuhao Chu^2,†

, Mina Wang¹, Bi Li², Pei Mao¹, Huazheng Zhang¹, Penglong Wang², Wenbo Guo², Liang Xu³, Liwei Ren¹, Haimin Lei^2,*

and Yuzhong Zhang^1,*

¹ Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China

² School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

³ The Second Affiliated Hospital of Shandong University of Chinese Medicine, Jinan 250001, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1599; https://doi.org/10.3390/molecules21111599 - 23 Nov 2016

Cited by 17 | Viewed by 5925

Abstract

Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods [...] Read more.

Hepatic fibrosis is a naturally occurring wound-healing reaction, with an imbalance of extracellular matrix (ECM) during tissue repair response, which can further deteriorate to hepatocellular carcinoma without timely treatment. Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing apoptosis are the main methods for the treatment of liver fibrosis. In our previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited more significant inhibitory activity against HepG2 cells and better hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However, inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was found that G-TOA could selectively inhibit the proliferation of activated HSC-T6 cells, induce morphological changes, early apoptosis, and mitochondrial membrane potential depolarization, increase intracellular free calcium levels, downregulate the expression of NF-κB/p65 and COX-2 protein, and decrease the ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided that it exerts anti-fibrosis effects on activated HSC-T6 cells. Full article

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15 pages, 1838 KiB

Open AccessReview

1-Deoxynojirimycin: Occurrence, Extraction, Chemistry, Oral Pharmacokinetics, Biological Activities and In Silico Target Fishing

by Kuo Gao^1,†, Chenglong Zheng^1,2,†, Tong Wang², Huihui Zhao¹, Juan Wang¹, Zhiyong Wang¹, Xing Zhai¹, Zijun Jia¹, Jianxin Chen¹, Yingwu Zhou^2,* and Wei Wang^1,*

¹ Beijing University of Chinese Medicine, Bei San Huan East Road, Beijing 100029, China

² Beijing Gulou Hospital of Traditional Chinese Medicine, 13 DouFuChi Hutong, Dongcheng District, Beijing 100009, China

^† These authors contributed equally to this work.

Molecules 2016, 21(11), 1600; https://doi.org/10.3390/molecules21111600 - 23 Nov 2016

Cited by 83 | Viewed by 14799

Abstract

1-Deoxynojirimycin (DNJ, C₆H₁₃NO₄, 163.17 g/mol), an alkaloid azasugar or iminosugar, is a biologically active natural compound that exists in mulberry leaves and Commelina communis (dayflower) as well as from several bacterial strains such as Bacillus and Streptomyces [...] Read more.

1-Deoxynojirimycin (DNJ, C₆H₁₃NO₄, 163.17 g/mol), an alkaloid azasugar or iminosugar, is a biologically active natural compound that exists in mulberry leaves and Commelina communis (dayflower) as well as from several bacterial strains such as Bacillus and Streptomyces species. Deoxynojirimycin possesses antihyperglycemic, anti-obesity, and antiviral features. Therefore, the aim of this detailed review article is to summarize the existing knowledge on occurrence, extraction, purification, determination, chemistry, and bioactivities of DNJ, so that researchers may use it to explore future perspectives of research on DNJ. Moreover, possible molecular targets of DNJ will also be investigated using suitable in silico approach. Full article

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10 pages, 1363 KiB

Open AccessArticle

Damxungmacin A and B, Two New Amicoumacins with Rare Heterocyclic Cores Isolated from Bacillus subtilis XZ-7

by Hui-Ling Tang^1,3

, Cheng-Hang Sun²

, Xin-Xin Hu², Xue-Fu You², Min Wang^1,* and Shao-Wei Liu^2,*

¹ School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

² Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

³ School of Pharmacy, Jiangsu Food & Pharmaceutical Science College, Huaian 223005, Jiangsu, China

Molecules 2016, 21(11), 1601; https://doi.org/10.3390/molecules21111601 - 23 Nov 2016

Cited by 8 | Viewed by 4875

Abstract

Two new amicoumacins, named Damxungmacin A (1) and B (2), were isolated from the culture broth of a soil-derived bacterium Bacillus subtilis XZ-7. Their chemical structures were elucidated by spectroscopic studies (UV, IR, NMR and HR-ESI-MS). Compound 1 possessed [...] Read more.

Two new amicoumacins, named Damxungmacin A (1) and B (2), were isolated from the culture broth of a soil-derived bacterium Bacillus subtilis XZ-7. Their chemical structures were elucidated by spectroscopic studies (UV, IR, NMR and HR-ESI-MS). Compound 1 possessed a 1,4-diazabicyclo[2.2.1]heptane-2-one ring system in its structure, which was reported for the first time, while 2 had a 1-acetylmorpholine-3-one moiety, which was naturally rare. Compound 1 exhibited moderate to weak cytotoxic activities against three human tumor cell lines (A549, HCT116 and HepG2) with IC₅₀ values of 13.33, 14.34 and 13.64 μM, respectively. Meanwhile, compound 1 showed weak antibacterial activities against some strains of Staphylococcus epidermidis, while compound 2 at 16 μg/mL did not show antibacterial activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 1951 KiB

Open AccessArticle

Investigating Glycol-Split-Heparin-Derived Inhibitors of Heparanase: A Study of Synthetic Trisaccharides

by Minghong Ni, Stefano Elli, Annamaria Naggi

, Marco Guerrini, Giangiacomo Torri and Maurice Petitou^*

Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, srl, via G. Colombo 81, 20133 Milano, Italy

Molecules 2016, 21(11), 1602; https://doi.org/10.3390/molecules21111602 - 23 Nov 2016

Cited by 18 | Viewed by 6213

Abstract

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their [...] Read more.

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose. As expected, in a heparanase inhibition assay, compound 2 is one order of magnitude more potent than 1. Using molecular modeling techniques we have created a 3D model of 1 and 2 that has been validated by NOESY NMR experiments. The pure synthetic oligosaccharides have allowed the first in depth study of the conformation of a glycol-split glucuronic acid. Introducing a glycol-split unit in the structure of 1 increases the conformational flexibility and shortens the distance between the two glucosamine motives, thus promoting interaction with heparanase. However, comparing the relative activities of 2 and roneparstat, we can conclude that the glycol-split motive is not the only determinant of the strong inhibitory effect of roneparstat. Full article

(This article belongs to the Collection Advances in Glycosciences)

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14 pages, 3301 KiB

Open AccessArticle

New Insights into the State Trapping of UV-Excited Thymine

by Ljiljana Stojanović¹, Shuming Bai¹, Jayashree Nagesh², Artur F. Izmaylov^2,3, Rachel Crespo-Otero⁴, Hans Lischka^5,6 and Mario Barbatti^1,*

¹ Aix Marseille Univ., CNRS, ICR, Marseille, France

² Chemical Physics Theory Group, Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada

³ Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada

⁴ School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK

⁵ School of Pharmaceutical Sciences and Technology, Tianjin University, Tianjin 300072, China

⁶ Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA

Molecules 2016, 21(11), 1603; https://doi.org/10.3390/molecules21111603 - 23 Nov 2016

Cited by 34 | Viewed by 10201

Abstract

After UV excitation, gas phase thymine returns to a ground state in 5 to 7 ps, showing multiple time constants. There is no consensus on the assignment of these processes, with a dispute between models claiming that thymine is trapped either in the [...] Read more.

After UV excitation, gas phase thymine returns to a ground state in 5 to 7 ps, showing multiple time constants. There is no consensus on the assignment of these processes, with a dispute between models claiming that thymine is trapped either in the first (S₁) or in the second (S₂) excited states. In the present study, a nonadiabatic dynamics simulation of thymine is performed on the basis of ADC(2) surfaces, to understand the role of dynamic electron correlation on the deactivation pathways. The results show that trapping in S₂ is strongly reduced in comparison to previous simulations considering only non-dynamic electron correlation on CASSCF surfaces. The reason for the difference is traced back to the energetic cost for formation of a CO π bond in S₂. Full article

(This article belongs to the Special Issue Experimental and Computational Photochemistry of Bioorganic Molecules)

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21 pages, 5935 KiB

Open AccessArticle

AutoDock-GIST: Incorporating Thermodynamics of Active-Site Water into Scoring Function for Accurate Protein-Ligand Docking

by Shota Uehara^* and Shigenori Tanaka^*

Department of Computational Science, Graduate School of System Informatics, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan

Molecules 2016, 21(11), 1604; https://doi.org/10.3390/molecules21111604 - 23 Nov 2016

Cited by 43 | Viewed by 15151

Abstract

Water plays a significant role in the binding process between protein and ligand. However, the thermodynamics of water molecules are often underestimated, or even ignored, in protein-ligand docking. Usually, the free energies of active-site water molecules are substantially different from those of waters [...] Read more.

Water plays a significant role in the binding process between protein and ligand. However, the thermodynamics of water molecules are often underestimated, or even ignored, in protein-ligand docking. Usually, the free energies of active-site water molecules are substantially different from those of waters in the bulk region. The binding of a ligand to a protein causes a displacement of these waters from an active site to bulk, and this displacement process substantially contributes to the free energy change of protein-ligand binding. The free energy of active-site water molecules can be calculated by grid inhomogeneous solvation theory (GIST), using molecular dynamics (MD) and the trajectory of a target protein and water molecules. Here, we show a case study of the combination of GIST and a docking program and discuss the effectiveness of the displacing gain of unfavorable water in protein-ligand docking. We combined the GIST-based desolvation function with the scoring function of AutoDock4, which is called AutoDock-GIST. The proposed scoring function was assessed employing 51 ligands of coagulation factor Xa (FXa), and results showed that both scoring accuracy and docking success rate were improved. We also evaluated virtual screening performance of AutoDock-GIST using FXa ligands in the directory of useful decoys-enhanced (DUD-E), thus finding that the displacing gain of unfavorable water is effective for a successful docking campaign. Full article

(This article belongs to the Collection Molecular Docking)

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10 pages, 789 KiB

Open AccessArticle

Chemical Constituents of Phaius mishmensis

by Chen-Wei Jao¹, Tzu-Heng Hung², Chi-Fen Chang^3,* and Ta-Hsien Chuang^2,4,*

¹ Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan

² School of Pharmacy, China Medical University, Taichung 40402, Taiwan

³ Department of Anatomy, School of Medicine, China Medical University, Taichung 40402, Taiwan

⁴ Research Center for Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan

Molecules 2016, 21(11), 1605; https://doi.org/10.3390/molecules21111605 - 23 Nov 2016

Cited by 22 | Viewed by 5135

Abstract

The partitioned n-hexane, CHCl₃, and EtOAc extracts from the crude MeOH extract of Phaius mishmensis showed considerable cytotoxicities against the human breast carcinoma (MCF-7), lung carcinoma (NCI-H460), and central nervous system carcinoma (SF-268) cell lines. Four new compounds, phaindole ( [...] Read more.

The partitioned n-hexane, CHCl₃, and EtOAc extracts from the crude MeOH extract of Phaius mishmensis showed considerable cytotoxicities against the human breast carcinoma (MCF-7), lung carcinoma (NCI-H460), and central nervous system carcinoma (SF-268) cell lines. Four new compounds, phaindole (1), (7′R,8′R)-phaithrene (2), methyl 3-hydroxy-4,5-dimethoxypropiophenone (3), and methyl hematinate (4), as well as 44 known compounds were isolated from the MeOH extract of Phaius mishmensis. The structures of the compounds were determined using spectroscopic methods. Full article

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16 pages, 2426 KiB

Open AccessArticle

The Draft Genome Sequence of Actinokineospora bangkokensis 44EHW^T Reveals the Biosynthetic Pathway of the Antifungal Thailandin Compounds with Unusual Butylmalonyl-CoA Extender Units

by Anja Greule¹, Bungonsiri Intra^2,3, Stephan Flemming¹, Marcel G. E. Rommel¹, Watanalai Panbangred^2,3 and Andreas Bechthold^1,*

¹ Department of Pharmaceutical Biology and Biotechnology, Institute of Pharmaceutical Sciences, Albert-Ludwigs-University of Freiburg, Stefan-Meier-Straße 19, 79104 Freiburg, Germany

² Department of Biotechnology, Faculty of Science, Mahidol University, 272 Rama 6 Road, Bangkok 10400, Thailand

³ Mahidol University and Osaka University Collaborative Research Center for Bioscience and Biotechnology, Bangkok 10400, Thailand

Molecules 2016, 21(11), 1607; https://doi.org/10.3390/molecules21111607 - 23 Nov 2016

Cited by 5 | Viewed by 7779

Abstract

We report the draft genome sequence of Actinokineospora bangkokensis 44EHW^T, the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There [...] Read more.

We report the draft genome sequence of Actinokineospora bangkokensis 44EHW^T, the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There are three gene clusters encoding large polyketide synthases of type I. Annotation of the ORF functions and targeted gene disruption enabled us to identify the cluster for thailandin biosynthesis. We propose a plausible biosynthetic pathway for thailandin, where the unusual butylmalonyl-CoA extender unit is incorporated and results in an untypical side chain. Full article

(This article belongs to the Special Issue Genomics-based Discovery of Microbial Natural Products)

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29 pages, 37116 KiB

Open AccessReview

Natural Compound Histone Deacetylase Inhibitors (HDACi): Synergy with Inflammatory Signaling Pathway Modulators and Clinical Applications in Cancer

by Hélène Losson¹, Michael Schnekenburger¹

, Mario Dicato¹ and Marc Diederich^2,*

¹ Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9 Rue Edward Steichen, Luxembourg L-2540, Luxembourg

² Department of Pharmacy, College of Pharmacy, Seoul National University, Building 29 Room 223, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea

Molecules 2016, 21(11), 1608; https://doi.org/10.3390/molecules21111608 - 23 Nov 2016

Cited by 62 | Viewed by 15006

Abstract

The remarkable complexity of cancer involving multiple mechanisms of action and specific organs led researchers Hanahan and Weinberg to distinguish biological capabilities acquired by cancer cells during the multistep development of human tumors to simplify its understanding. These characteristic hallmarks include the abilities [...] Read more.

The remarkable complexity of cancer involving multiple mechanisms of action and specific organs led researchers Hanahan and Weinberg to distinguish biological capabilities acquired by cancer cells during the multistep development of human tumors to simplify its understanding. These characteristic hallmarks include the abilities to sustain proliferative signaling, evade growth suppressors, resist cell death, enable replicative immortality, induce angiogenesis, activate invasion and metastasis, avoid immune destruction, and deregulate cellular energetics. Furthermore, two important characteristics of tumor cells that facilitate the acquisition of emerging hallmarks are tumor-promoting inflammation and genome instability. To treat a multifactorial disease such as cancer, a combination treatment strategy seems to be the best approach. Here we focus on natural histone deacetylase inhibitors (HDACi), their clinical uses as well as synergies with modulators of the pro-inflammatory transcription factor signaling pathways. Full article

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

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14 pages, 969 KiB

Open AccessArticle

Simultaneous Ultra Performance Liquid Chromatography Determination and Antioxidant Activity of Linarin, Luteolin, Chlorogenic Acid and Apigenin in Different Parts of Compositae Species

by Seung Hwan Hwang¹, Ji Hun Paek¹ and Soon Sung Lim^1,2,*

¹ Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

² Institute of Natural Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

Molecules 2016, 21(11), 1609; https://doi.org/10.3390/molecules21111609 - 23 Nov 2016

Cited by 19 | Viewed by 6865

Abstract

Linarin (LA), luteolin (LE), chlorogenic acid (CA) and apigenin (AP) are four major flavonoids with various promising bioactivities found in Compositae (COP) species. A reliable, reproducible and accurate method for the simultaneous and quantitative determination of these four major flavonoids by Ultra Performance [...] Read more.

Linarin (LA), luteolin (LE), chlorogenic acid (CA) and apigenin (AP) are four major flavonoids with various promising bioactivities found in Compositae (COP) species. A reliable, reproducible and accurate method for the simultaneous and quantitative determination of these four major flavonoids by Ultra Performance Liquid Chromatography (UPLC) analysis was developed. This method should be appropriate for the quality assurance of COP. The UPLC separation was carried out using an octadecylsilane (ODS) Hypersil (2.1 mm × 250 mm, 1.9 μm) and a mobile phase composed of acetonitrile and 0.1% formic acid in water at a flow rate 0.44 mL/min and ultraviolet (UV) detection 254 nm. Gradient elution was employed. The method was precise, with relative standard deviation below 3.0% and showed excellent linearity (R² > 0.999). The recoveries for the four flavonoids in COP were between 95.49%–106.23%. The average contents of LA, LE, CA and AP in different parts (flower, leave and stem) of COP were between 0.64–1.47 g/100 g, 0.66–0.89 g/100 g, 0.32–0.52 g/100 g and 0.16–0.18 g/100 g, respectively. The method was accurate and reproducible and it can provide a quantitative basis for quality control of COP. Full article

(This article belongs to the Special Issue Structure, Chemical Analysis, Biosynthesis, Metabolism, Molecular Engineering and Biological Functions of Phytoalexins)

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