Molecules

13 pages, 256 KiB

Open AccessArticle

Chokeberry Pomace as a Determinant of Antioxidant Parameters Assayed in Blood and Liver Tissue of Polish Merino and Wrzosówka Lambs

by Paulina Lipińska^1,*, Atanas G. Atanasov^1,2

, Marek Palka³ and Artur Jóźwik¹

¹ Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland

² Department of Pharmacognosy, University of Vienna, 1090 Vienna, Austria

³ Faculty of Power and Aeronautical Engineering, Warsaw University of Technology, 00-665 Warsaw, Poland

Molecules 2017, 22(11), 1461; https://doi.org/10.3390/molecules22111461 - 7 Nov 2017

Cited by 18 | Viewed by 4671

Abstract

Despite being a plant by-product, chokeberry pomace is believed to exert some therapeutic effects because it is one of the richest sources of highly bioavailable non-enzymatic antioxidants. The aim of this study was to determine the functionality of bioactive compounds present in the [...] Read more.

Despite being a plant by-product, chokeberry pomace is believed to exert some therapeutic effects because it is one of the richest sources of highly bioavailable non-enzymatic antioxidants. The aim of this study was to determine the functionality of bioactive compounds present in the Aronia melanocarpa pomace (chokeberry) based on enzymatic and non-enzymatic parameters related to the active defence of liver and blood against the effects of oxidative stress. The experiment was conducted with 48 lambs of two breeds—Polish Merino and Wrzosówka. Experimental groups were administered the basic feed with the addition of 150 g or 300 g of black chokeberry pomace per each kg of the complete feed. The activities of antioxidative enzymes (superoxide dismutase, glutathione peroxidase), peptides (glutathione, glutathione disulfide), and a lipid peroxidation indicator (malondialdehyde), as well as the capacity of non-enzymatic antioxidants were investigated. The results proved a strong effect of bioactive compounds contained in the black chokeberry pomace on the estimated parameters. The inclusion of chokeberry pomace in feed mixtures brought many benefits linked with the antioxidative protection. Parameters responsible for the oxidative status were significantly modified despite the commonly-held view about a limited possibility of transferring phenolic compounds to the organs. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

21 pages, 2292 KiB

Open AccessArticle

Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis

by Nadjet Rezki^1,2,*, Salsabeel A. Al-Sodies¹

, Sheikh Shreaz³, Rayees Ahmad Shiekh^1,4, Mouslim Messali¹, Vaseem Raja⁵ and Mohamed R. Aouad^1,2,*

¹ Department of Chemistry, Faculty of Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 30002, Saudi Arabia

² Laboratoire de Chimie et Electrochimie des Complexes Métalliques (LCECM) USTO-MB, Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf, P.O. Box 1505, El M`nouar, Oran 31000, Algeria

³ Environment and Life Sciences Research Center, Kuwait Institute for Scientific Research, P.O. Box 24885, Safat 13109, Kuwait

⁴ Government Degree College Pulwama, University of Kashmir, Srinagar 192301, India

⁵ Department of Applied Sciences & Humanities, Faculty of Engineering & Technology, Jamia Millia Islamia, Central University, New Delhi 110025, India

Molecules 2017, 22(11), 1532; https://doi.org/10.3390/molecules22111532 - 7 Nov 2017

Cited by 15 | Viewed by 4164

Abstract

A series of specific task ionic liquids (ILs) based on a pyridiniumhydrazone scaffold in combination with hexafluorophosphate (PF₆⁻), tetrafluoroboron (BF₄⁻) and/or trifluoroacetate (CF₃COO⁻) counter anion, were designed and characterized by IR, NMR and [...] Read more.

A series of specific task ionic liquids (ILs) based on a pyridiniumhydrazone scaffold in combination with hexafluorophosphate (PF₆⁻), tetrafluoroboron (BF₄⁻) and/or trifluoroacetate (CF₃COO⁻) counter anion, were designed and characterized by IR, NMR and mass spectrometry. The reactions were conducted under both conventional and green ultrasound procedures. The antifungal potential of the synthesized compounds 2–25 was investigated against 40 strains of Candida (four standard and 36 clinical isolates). Minimum inhibitory concentrations (MIC₉₀) of the synthesized compounds were in the range of 62.5–2000 μg/mL for both standard and oral Candida isolates. MIC₉₀ results showed that the synthesized 1-(2-(4-chlorophenyl)-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-pyridin-1-ium hexafluorophosphate (11) was found to be most effective, followed by 4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-1-(2-(4-nitrophenyl)-2-oxoethyl)-pyridin-1-ium hexafluorophosphate (14) and 1-(2-ethoxy-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)pyridin-1-ium hexafluorophosphate (8). All the Candida isolates showed marked sensitivity towards the synthesized compounds. Ergosterol content was drastically reduced by more active synthesized compounds, and agreed well with MIC₉₀ values. Confocal scanning laser microscopy (CLSM) results showed that the red colored fluorescent dye enters the test agent treated cells, which confirms cell wall and cell membrane damage. The microscopy results obtained suggested membrane-located targets for the action of these synthesized compounds. It appears that the test compounds might be interacting with ergosterol in the fungal cell membranes, decreasing the membrane ergosterol content and ultimately leading to membrane disruption as visible in confocal results. The present study indicates that these synthesized compounds show significant antifungal activity against Candida which forms the basis to carry out further in vivo experiments before their clinical use. Full article

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12 pages, 2705 KiB

Open AccessArticle

Preparation and Bioactivity Assessment of Chitosan-1-Acetic Acid-5-Flurouracil Conjugates as Cancer Prodrugs

by Mohsin O. Mohammed^1,*

, Kameran S. Hussain² and Nadia Q. Haj¹

¹ Department of Chemistry, College of Science, Kirkuk University, Kirkuk 00964, Iraq

² Department of Chemistry, College of Nursing, Kirkuk University, Kirkuk 00964, Iraq

Molecules 2017, 22(11), 1629; https://doi.org/10.3390/molecules22111629 - 8 Nov 2017

Cited by 18 | Viewed by 7001

Abstract

5-fluorouracil (5-FU) is a specific anti-cancer agent that is generally used to treat gastrointestinal, colorectal, and breast cancer. In this work, chitosan (CS) was extracted from local fish scales using an established method. 5-FU was then converted to 1-acetic acid-5-fluorouracil (FUAC) and reacted [...] Read more.

5-fluorouracil (5-FU) is a specific anti-cancer agent that is generally used to treat gastrointestinal, colorectal, and breast cancer. In this work, chitosan (CS) was extracted from local fish scales using an established method. 5-FU was then converted to 1-acetic acid-5-fluorouracil (FUAC) and reacted with this CS to prepare chitosan-1-acetic acid-5-fluorouracil (CS-FUAC) conjugates as a colon-specific prodrug. All compounds were characterized by Proton nuclear magnetic resonance (¹H-NMR), Fourier-transform infrared (FTIR), and UV-visible spectroscopy. The synthesized compound was subjected to a chemical stability study in phosphate buffer (0.2 M, pH 7.4) and in KCl/HCl buffer (0.2 M, pH 1.2) at different time intervals (0–240 min) and incubation at 37 °C. This revealed a significantly greater stability and a longer half-life for the CS-FUAC than for FUAC. Hemolytic activity results indicated a much lower toxicity for CS-FUAC than for 5-FU and supported consideration of CS-FUAC for further biological screening and application trials. The percentage of FUAC in the conjugates was determined by subjecting the prodrug to treatment in basic media to hydrolyze the amide bond, followed by absorbency measurements at 273 nm. The cytotoxicity studies of the conjugates were also evaluated on human colorectal cancer cell line (HT-29), which showed that the conjugates are more cytotoxic than the free drug. Therefore, CS-FUAC conjugates can be considered to represent potential colon-specific drug delivery agents, with minimal undesirable side effects, for colon cancer therapy. Full article

(This article belongs to the Special Issue Synthesis and Biological Applications of Glycoconjugates)

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14 pages, 2351 KiB

Open AccessArticle

Synthesis, Cytotoxicity and Molecular Docking Studies of the 9-Substituted 5-Styryltetrazolo[1,5-c]quinazoline Derivatives

by Malose J. Mphahlele^1,*

, Samantha Gildenhuys²

and Nishal Parbhoo²

¹ Department of Chemistry, University of South Africa, Private Bag X06, Florida 1710, South Africa

² Department of Life & Consumer Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa

Molecules 2017, 22(11), 1719; https://doi.org/10.3390/molecules22111719 - 26 Oct 2017

Cited by 8 | Viewed by 3877

Abstract

In this paper, we describe the synthesis of the 5-styryltetrazolo[1,5-c]quinazolines substituted at the 9-position with a 4-fluorophenyl ring directly or via a conjugated π-spacer (C=C or C≡C bond) based on the 6-bromo-4-chloro-2-styrylquinazoline scaffold. The structures of the synthesized compounds were characterized [...] Read more.

In this paper, we describe the synthesis of the 5-styryltetrazolo[1,5-c]quinazolines substituted at the 9-position with a 4-fluorophenyl ring directly or via a conjugated π-spacer (C=C or C≡C bond) based on the 6-bromo-4-chloro-2-styrylquinazoline scaffold. The structures of the synthesized compounds were characterized based on a combination of ¹H-NMR, ¹³C-NMR, IR and high resolution mass spectral data as well as microanalyses. The tetrazoloquinazolines were evaluated for potential in vitro cytotoxicity against the human breast adenocarcinoma (MCF-7) and cervical cancer (HeLa) cells. The anti-proliferative assays demonstrated that the 9-bromo-5-styryltetrazolo[1,5-c]quinazoline 3a and 9-bromo-5-(4-fluorostyryl)tetrazolo[1,5-c]quinazoline 3b exhibit significant cytotoxicity against both cell lines. A carbon-based substituent at the 9-position resulted in complete loss of cytotoxicity against both cell lines except for the 5,9-bis((E)-4-fluorostyryl)tetrazolo[1,5-c]quinazoline 4e, which was found to exhibit comparable cytotoxicity to that of Melphalan (IC₅₀ = 61 μM) against the MCF-7 cell line with IC₅₀ value of 62 μM. Molecular docking against tubulin (PDB:1TUB) showed that compounds 3a, 3b and 4e bind to the tubulin heterodimer. Binding involves hydrogen bonding for 3a and 3b and halogen interactions for 4e. Full article

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14 pages, 2562 KiB

Open AccessArticle

Additivity vs Synergism: Investigation of the Additive Interaction of Cinnamon Bark Oil and Meropenem in Combinatory Therapy

by Shun-Kai Yang¹

, Khatijah Yusoff², Chun-Wai Mai⁴

, Wei-Meng Lim⁵, Wai-Sum Yap⁶, Swee-Hua Erin Lim^3,7

and Kok-Song Lai^1,*

¹ Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

² Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

³ Perdana University-Royal College of Surgeons in Ireland, Perdana University, MAEPS Building, Serdang, Selangor, Malaysia

⁴ Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia

⁵ Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia

⁶ Department of Biotechnology, Faculty of Applied Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia

⁷ Health Sciences Division, Abu Dhabi Women’s College, Higher Colleges of Technology, 41012 Abu Dhabi, United Arab Emirates

Molecules 2017, 22(11), 1733; https://doi.org/10.3390/molecules22111733 - 4 Nov 2017

Cited by 66 | Viewed by 6831

Abstract

Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their [...] Read more.

Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 4643 KiB

Open AccessArticle

Design, Synthesis, and Evaluation of Novel Phenolic Acid/Dipeptide/Borneol Hybrids as Potent Angiotensin Converting Enzyme (ACE) Inhibitors with Anti-hypertension Activity

by Ying Sun^1,†, Yujun Bai^1,†, Xirui He¹, Yajun Bai^1,2, Pei Liu¹, Zefeng Zhao¹, Xufei Chen¹ and Xiaohui Zheng^1,*

¹ Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an 710069, China

² Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi’an 710127, China

^† These authors contributed equally to this paper and share co-first authorship.

Molecules 2017, 22(11), 1739; https://doi.org/10.3390/molecules22111739 - 3 Nov 2017

Cited by 10 | Viewed by 6173 | Correction

Abstract

Under the guidance of combination of traditional Chinese medicine chemistry (CTCMC), this study describes the preparation of a phenolic acid/dipeptide/borneol hybrid consisting of phenolic acid and a bornyl moiety connected to the dipeptide N-terminal and C-terminal respectively. It also evaluates their angiotensin converting [...] Read more.

Under the guidance of combination of traditional Chinese medicine chemistry (CTCMC), this study describes the preparation of a phenolic acid/dipeptide/borneol hybrid consisting of phenolic acid and a bornyl moiety connected to the dipeptide N-terminal and C-terminal respectively. It also evaluates their angiotensin converting enzyme (ACE) inhibitory and synergistic antihypertensive activities. Briefly, a series of novel phenolic acid/dipeptide/borneol hybrids were prepared and investigated for their ability to inhibit ACE. The influence of the phenolic acid and bornyl moiety on subsite selectivity is also demonstrated. Among all the new compounds, two compounds—7a and 7g—reveal good inhibition potency in in vitro ACE-inhibitory tests. Interestingly, favorable binding results in molecular docking studies also supported the in vitro results. Additionally, the bioassay showed that oral administration of the two compounds displayed high and long-lasting antihypertensive activity both in acute antihypertensive tests and in therapeutic antihypertensive tests by non-invasive blood pressure measurements in spontaneously hypertensive rats. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1221 KiB

Open AccessArticle

Anti-HIV Activity of Ocimum labiatum Extract and Isolated Pheophytin-a

by Petrina Kapewangolo^1,2

, Martha Kandawa-Schulz² and Debra Meyer^1,3,*

¹ Department of Biochemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0002, South Africa

² Department of Chemistry and Biochemistry, Faculty of Science, University of Namibia, P/Bag 13301, Windhoek 9000, Namibia

³ Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, Johannesburg 2006, South Africa

Molecules 2017, 22(11), 1763; https://doi.org/10.3390/molecules22111763 - 6 Nov 2017

Cited by 19 | Viewed by 5752

Abstract

Ocimum plants are traditionally used to manage HIV/AIDS in various African countries. The effects of Ocimum labiatum extract on HIV-1 protease (PR) and reverse transcriptase (RT) is presented here along with characterization of an identified bioactive compound, achieved through ¹H- and ¹³ [...] Read more.

Ocimum plants are traditionally used to manage HIV/AIDS in various African countries. The effects of Ocimum labiatum extract on HIV-1 protease (PR) and reverse transcriptase (RT) is presented here along with characterization of an identified bioactive compound, achieved through ¹H- and ¹³C-NMR. The extract’s effect on HIV-1 replication was assessed by HIV-1 p24 antigen capture. Cytotoxicity of samples was evaluated using tetrazolium dyes and real-time cell electronic sensing (RT-CES). Ocimum labiatum inhibited HIV-1 PR with an IC₅₀ value of 49.8 ± 0.4 μg/mL and presented weak inhibition (21%) against HIV-1 RT. The extract also reduced HIV-1 replication in U1 cells at a non-cytotoxic concentration (25 μg/mL). The CC₅₀ value of the extract in U1 cells was 42.0 ± 0.13 μg/mL. The HIV-1 PR inhibiting fraction was purified using prep-HPLC and yielded a chlorophyll derivative, pheophytin-a (phy-a). Phy-a inhibited HIV-1 PR with an IC₅₀ value of 44.4 ± 1.5 μg/mL (51 ± 1.7 μM). The low cytotoxicity of phy-a in TZM-bl cells was detected by RT-CES and the CC₅₀ value in U1 cells was 51.3 ± 1.0 μg/mL (58.9 ± 1.2 μM). This study provides the first in vitro evidence of anti-HIV activity of O. labiatum and isolated phy-a, supporting further investigation of O. labiatum for lead compounds against HIV-1. Full article

(This article belongs to the Collection Herbal Medicine Research)

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10 pages, 1645 KiB

Open AccessArticle

Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes

by Lucas De Abreu Costa^1,2, Marcelo Henrique Fernandes Ottoni^1,3

, Michaelle Geralda Dos Santos^1,3, Agnes Batista Meireles^1,2, Valéria Gomes de Almeida^1,3, Wagner De Fátima Pereira¹, Bethânia Alves de Avelar-Freitas^1,3,* and Gustavo Eustáquio Alvim Brito-Melo^1,2,3

¹ Immunology Laboratory, Integrated Center for Health Research, Federal University of the Jequitinhonha and Mucuri Valleys (UFVJM), Diamantina, MG 39100-000, Brazil

² Multicenter Graduate Program in Physiological Sciences/UFVJM Graduate Program in Pharmaceutical Sciences/UFVJM, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, MG 39100-000, Brazil

³ Institute of Science and Technology, Federal University of the Jequitinhonha and Mucuri Valleys, Diamantina, MG 39100-000, Brazil

Molecules 2017, 22(11), 1789; https://doi.org/10.3390/molecules22111789 - 10 Nov 2017

Cited by 136 | Viewed by 17030

Abstract

Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs [...] Read more.

Dimethylsulfoxide (DMSO) is an amphipathic molecule composed of a polar domain characterized by the sulfinyl and two nonpolar methyl groups, for this reason it is able to solubilize polar and nonpolar substances and transpose hydrophobic barriers. DMSO is widely used to solubilize drugs of therapeutic applications and studies indicated that 10% v/v concentration did not modify culture viability when used to treat human peripheral blood mononuclear cells (PBMC). However, some DMSO concentrations could influence lymphocyte activation and present anti-inflammatory effects. Therefore, the objective of this study was to evaluate the effect of DMSO on lymphocyte activation parameters. Cell viability analysis, proliferation, and cytokine production were performed on PBMC from six healthy subjects by flow cytometry. The results indicated that 2.5% v/v DMSO concentrations did not modify lymphocytes viability. DMSO at 1% and 2% v/v concentrations reduced the relative proliferation index of lymphocytes and at 5% and 10% v/v concentrations reduced the percentage of total lymphocytes, cluster of differentiation 4⁺ (CD4⁺) T lymphocytes and CD8⁺ T lymphocytes interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) producers. Thus, it was concluded that DMSO has an in vitro anti-inflammatory effect by reducing lymphocyte activation demonstrated with proliferation reduction and the decrease of cytokine production. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

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13 pages, 2408 KiB

Open AccessArticle

Encapsulation Mechanism of Oxyresveratrol by β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin and Computational Analysis

by Jianfei He¹, Zong-Ping Zheng^2,*

, Qin Zhu³, Fengxian Guo² and Jie Chen^1,*

¹ State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China

² Fujian Province Key Laboratory for the Development of Bioactive Material from Marine Alge, College of Oceanology and Food Science, Quanzhou Normal University, Quanzhou 362000, China

³ Key Lab of Medical Plant Genetic Improvement and Quality Control of Zhejiang Province, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China

Molecules 2017, 22(11), 1801; https://doi.org/10.3390/molecules22111801 - 31 Oct 2017

Cited by 37 | Viewed by 10070

Abstract

In this study, the encapsulation mechanism of oxyresveratrol and β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was studied. As this research shows, oxyresveratrol and two cyclodextrins (CDs) were able to form inclusion complexes in a 1:1 stoichiometry. However, the interaction with HP-β-CD was more efficient, [...] Read more.

In this study, the encapsulation mechanism of oxyresveratrol and β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was studied. As this research shows, oxyresveratrol and two cyclodextrins (CDs) were able to form inclusion complexes in a 1:1 stoichiometry. However, the interaction with HP-β-CD was more efficient, showing up as higher encapsulation constant (K_F) (35,864.72 ± 3415.89 M⁻¹). The K_F values exhibited a strong dependence on temperature and pH, which decreased as they increased. From the thermodynamic parameters (ΔH⁰, ΔS⁰, and ΔG⁰) of the oxyresveratrol loaded β-CD (oxyresveratrol-β-CD) and HP-β-CD (oxyresveratrol-HP-β-CD), it could be seen that the complexation process was spontaneous and exothermic, and the main driving forces between oxyrsveratrol and CDs were hydrogen bonding and van der waals force. Besides, molecular docking combined with ¹H-NMR were used to explain the most possible mode of interactions between oxyresveratrol and CDs. Full article

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14 pages, 1437 KiB

Open AccessArticle

Simultaneous Determination of Seven Anthraquinone Aglycones of Crude and Processed Semen Cassiae Extracts in Rat Plasma by UPLC–MS/MS and Its Application to a Comparative Pharmacokinetic Study

by Rixin Guo^1,†, Hongwei Wu^1,†, Xiankuo Yu¹, Mengying Xu², Xiao Zhang², Liying Tang^1,* and Zhuju Wang^1,*

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, No. 16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, China

² School of Medicine, Henan University of Chinese Medicine, No. 156 Jinshuidong Ave., Zhengzhou 450046, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1803; https://doi.org/10.3390/molecules22111803 - 28 Oct 2017

Cited by 32 | Viewed by 5203

Abstract

Semen cassiae is the ripe seed of Cassia obtusifolia L. or Cassia tora L. of the family Leguminosae. In traditional Chinese medicine, the two forms of Semen cassiae are raw Semen cassiae (R-SC) and parched Semen cassiae (P-SC). To clarify the processing mechanism [...] Read more.

Semen cassiae is the ripe seed of Cassia obtusifolia L. or Cassia tora L. of the family Leguminosae. In traditional Chinese medicine, the two forms of Semen cassiae are raw Semen cassiae (R-SC) and parched Semen cassiae (P-SC). To clarify the processing mechanism of Semen cassiae, the pharmacokinetics of R-SC and P-SC extracts were examined. A simple, rapid, sensitive ultra-high-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the simultaneous determination of seven anthraquinone aglycones of Semen cassiae (aurantio-obtusin, obtusifolin, questin, 2-hydroxyemodin-1-methyl-ether, rhein, emodin, 1,2,7-trimethoxyl-6,8-dihydroxy-3-methylanthraquinone) to compare the pharmacokinetics of raw and parched Semen cassiae in rat plasma. Compared with the R-SC group, C_max and AUC_0-12 tended to be higher in the P-SC group. In particular, C_max values for aurantio-obtusin, obtusifolin, questin, 2-hydroxyemodin-1-methyl-ether and rhein were significantly higher in the P-SC group (p < 0.05). Meanwhile, T_max and MRT_0-12 tended to be lower in the P-SC group. Specifically, T_max for aurantio-obtusin and 2-hydroxyemodin-1-methyl-ether and MRT_0-12 for obtusifolin and rhein were significantly higher in the P-SC group (p < 0.05). Full article

(This article belongs to the Collection Herbal Medicine Research)

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10 pages, 1516 KiB

Open AccessArticle

A Search for Dual Action HIV-1 Reverse Transcriptase, Bacterial RNA Polymerase Inhibitors

by Agata Paneth^1,*

, Tomasz Frączek², Agnieszka Grzegorczyk³

, Dominika Janowska¹, Anna Malm³ and Piotr Paneth^2,*

¹ Department of Organic Chemistry, Medical University of Lublin, 20-093 Lublin, Poland

² Institute of Applied Radiation Chemistry, Lodz University of Technology, 90-924 Lodz, Poland

³ Department of Pharmaceutical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland

Molecules 2017, 22(11), 1808; https://doi.org/10.3390/molecules22111808 - 25 Oct 2017

Cited by 3 | Viewed by 4031

Abstract

Using molecular modeling approach, potential antibacterial agents with triazole core were proposed. A moderate to weak level of antibacterial activity in most of the compounds have been observed, with best minimal inhibitory concentration (MIC) value of 0.003 mg/mL, as shown by the 15 [...] Read more.

Using molecular modeling approach, potential antibacterial agents with triazole core were proposed. A moderate to weak level of antibacterial activity in most of the compounds have been observed, with best minimal inhibitory concentration (MIC) value of 0.003 mg/mL, as shown by the 15 against S. epidermidis. Studied compounds were also submitted to the antifungal assay. The best antifungal activity was detected for 16 with MIC at 0.125 and 0.25 mg/mL against C. albicans and C. parapsilosis, respectively. Full article

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14 pages, 4598 KiB

Open AccessArticle

Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats

by Peng Jiang¹, Xiuwen Zhang², Yutong Huang¹, Nengneng Cheng^1,* and Yueming Ma³

¹ Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China

² Department of Pharmacy, Eye Ear Nose Throat Hospital of Fudan University, Shanghai 200031, China

³ Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Molecules 2017, 22(11), 1809; https://doi.org/10.3390/molecules22111809 - 25 Oct 2017

Cited by 20 | Viewed by 6083

Abstract

Our previous study showed that kurarinone was the main hepatotoxic ingredient of Sophora flavescens, accumulating in the liver. This study characterized the mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation [...] Read more.

Our previous study showed that kurarinone was the main hepatotoxic ingredient of Sophora flavescens, accumulating in the liver. This study characterized the mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic accumulation of kurarinone. ESF impaired hepatic function and caused fat accumulation in the liver after oral administration (1.25 and 2.5 g/kg for 14 days in rats). Serum metabolomics evaluation based on high-resolution mass spectrometry was conducted and real-time PCR was used to determine the expression levels of CPT-1, CPT-2, PPAR-α, and LCAD genes. Effects of kurarinone on triglyceride levels were evaluated in HL-7702 cells. Tissue distribution of kurarinone and kurarinone glucuronides was analyzed in rats receiving ESF (2.5 g/kg). Active uptake of kurarinone and kurarinone glucuronides was studied in OAT2-, OATP1B1-, OATP2B1-, and OATP1B3-transfected HEK293 cells. Our results revealed that after oral administration of ESF in rats, kurarinone glucuronides were actively transported into hepatocytes by OATP1B3 and hydrolyzed into kurarinone, which inhibited fatty acid β-oxidation through the reduction of l-carnitine and the inhibition of PPAR-α pathway, ultimately leading to lipid accumulation and liver injury. These findings contribute to understanding hepatotoxicity of kurarinone after oral administration of ESF. Full article

(This article belongs to the Collection Herbal Medicine Research)

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18 pages, 5893 KiB

Open AccessArticle

Synthesis, Structure, Surface and Antimicrobial Properties of New Oligomeric Quaternary Ammonium Salts with Aromatic Spacers

by Bogumił Brycki^1,*, Anna Koziróg²

, Iwona Kowalczyk¹, Tomasz Pospieszny¹, Paulina Materna¹ and Jędrzej Marciniak³

¹ Laboratory of Microbiocides Chemistry, Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61-614 Poznań, Poland

² Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wólczańska 171/173, 90-924 Łódź, Poland

³ Department of Materials Chemistry, Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b, 61-614 Poznań, Poland

Molecules 2017, 22(11), 1810; https://doi.org/10.3390/molecules22111810 - 25 Oct 2017

Cited by 32 | Viewed by 7624

Abstract

New dimeric, trimeric and tetrameric quaternary ammonium salts were accomplished by reaction of tertiary alkyldimethyl amines with appropriate bromomethylbenzene derivatives. A series of new cationic surfactants contain different alkyl chain lengths (C4–C18), aromatic spacers and different numbers of quaternary nitrogen atoms. The structure [...] Read more.

New dimeric, trimeric and tetrameric quaternary ammonium salts were accomplished by reaction of tertiary alkyldimethyl amines with appropriate bromomethylbenzene derivatives. A series of new cationic surfactants contain different alkyl chain lengths (C4–C18), aromatic spacers and different numbers of quaternary nitrogen atoms. The structure of the products was confirmed by spectral analysis (FT-IR, ¹H-NMR, ¹³C-NMR and 2D-NMR), mass spectroscopy (ESI-MS), elemental analysis, as well as PM5 semiempirical methods. Compound (21) was also analyzed using X-ray crystallography. Critical micelle concentration (CMC) of 1,4-bis-[N-(1-alkyl)-N,N-dimethylammoniummethyl]benzene dibromides (3–9) was determined to characterize the aggregation behavior. The antimicrobial properties of novel QACs (Quaternary Ammonium Salts) were examined to set their minimal inhibitory concentration (MIC) values against fungi Aspergillus niger, Candida albicans, Penicillium chrysogenum and bacteria Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. Full article

(This article belongs to the Section Organic Chemistry)

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17 pages, 2728 KiB

Open AccessArticle

Design, Synthesis and Bioactivity Evaluation of Novel β-carboline 1,3,4-oxadiazole Derivatives

by Zhi-Jun Zhang^1,2

, Jing-Jing Zhang^1,2

, Zhi-Yan Jiang^1,2 and Guo-Hua Zhong^1,2,*

¹ Key Laboratory of Natural Pesticide and Chemical Biology, Ministry of Education, Guangzhou 510642, China

² Lab of Insect Toxicology, South China Agricultural University, Guangzhou 510642, China

Molecules 2017, 22(11), 1811; https://doi.org/10.3390/molecules22111811 - 29 Oct 2017

Cited by 17 | Viewed by 4557

Abstract

A series of novel β-carboline 1,3,4-oxadiazole derivatives were designed and synthesized, and the in vitro cytotoxic activity against Sf9 cells and growth inhibitory activity against Spodoptera litura were evaluated. Bioassay results showed that most of these compounds exhibited excellent in vitro cytotoxic activity. [...] Read more.

A series of novel β-carboline 1,3,4-oxadiazole derivatives were designed and synthesized, and the in vitro cytotoxic activity against Sf9 cells and growth inhibitory activity against Spodoptera litura were evaluated. Bioassay results showed that most of these compounds exhibited excellent in vitro cytotoxic activity. Especially, compound 37 displayed the best efficacy in vitro (IC₅₀ = 3.93 μM), and was five-fold more potent than camptothecin (CPT) (IC₅₀ = 18.95 μM). Moreover, compounds 5 and 37 could induce cell apoptosis and cell cycle arrest and stimulate Sf-caspase-1 activation in Sf9 cells. In vivo bioassay also demonstrated that compounds 5 and 37 could significantly inhibit larvae growth of S. litura with decreasing the weight of larvae and pupae. Based on these bioassay results, compounds 5 and 37 emerged as lead compounds for the development of potential insect growth inhibitions. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2489 KiB

Open AccessArticle

Solvent and Copper Ion-Induced Synthesis of Pyridyl–Pyrazole-3-One Derivatives: Crystal Structure, Cytotoxicity

by Qiu Ping Huang^1,2,†, Shao Nan Zhang^1,†, Shu Hua Zhang^1,*

, Kai Wang¹ and Yu Xiao^1,*

¹ Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, Collaborative Innovation Center for Exploration of Hidden Nonferrous Metal Deposits and Development of New Materials in Guangxi (College of Chemistry and Bioengineering), Guilin University of Technology, Guilin 541004, China

² College of Chemistry and Engineering, Guangxi Normal University for Nationalities, Chongzuo 532200, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1813; https://doi.org/10.3390/molecules22111813 - 25 Oct 2017

Cited by 13 | Viewed by 4746

Abstract

Five novel compounds, methyl 5-(acetyloxy)-1-(6-bromo-2-pyridinyl)-1H-pyrazole-3-carboxylate (1), methyl 1-(6-bromo-2-pyridinyl)-5-hydroxy-1H-pyrazole-3-carboxylate (2), Trimethyl 1,1′,1′′-tris(6-bromo-2-pyridinyl)-5,5′′-dihydroxy-5′-oxo-1′,5′-dihydro-1H,1′′H-4,4′: 4′,4′′-terpyrazole-3,3′,3′′-tricarboxylate (H₂L¹, 3), [Cu₂(L²)₂]·CH₃OH (4), H₂L^2A·CH₃ [...] Read more.

Five novel compounds, methyl 5-(acetyloxy)-1-(6-bromo-2-pyridinyl)-1H-pyrazole-3-carboxylate (1), methyl 1-(6-bromo-2-pyridinyl)-5-hydroxy-1H-pyrazole-3-carboxylate (2), Trimethyl 1,1′,1′′-tris(6-bromo-2-pyridinyl)-5,5′′-dihydroxy-5′-oxo-1′,5′-dihydro-1H,1′′H-4,4′: 4′,4′′-terpyrazole-3,3′,3′′-tricarboxylate (H₂L¹, 3), [Cu₂(L²)₂]·CH₃OH (4), H₂L^2A·CH₃CN (5) were synthesized. Compounds 1–5 characterized by elemental analysis, IR, and X-ray single-crystal diffraction. And 1–3 were also characterized by ¹H NMR, ¹³C NMR and ESI-MS. The H₂L¹, H₂L² were formed by in-situ reaction. H₂L² and H₂L^2A are mesomer compounds which have two chiral carbons. The antitumor activity of compounds 1–5 against BEL-7404, HepG2, NCI-H460, T-24, A549 tumor cell lines were screened by methylthiazolyl tetrozolium (MTT) assay. The compounds 1, 2 showed weakly growth inhibition on the HepG2 cell lines. The HepG2 and A549 cell lines showed higher sensitivity to compound 4, while the IC₅₀ values are 10.66, 28.09 μM, respectively. It is worth noting that compounds 1–5 did not show cytotoxicity to human normal liver cell line HL-7702, suggesting its cytotoxic selectivity on these tumor cell lines. Full article

(This article belongs to the Special Issue Pyrazole Derivatives)

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11 pages, 3170 KiB

Open AccessArticle

Anticancer Effects of Resveratrol-Loaded Solid Lipid Nanoparticles on Human Breast Cancer Cells

by Wenrui Wang¹, Lingyu Zhang², Tiantian Chen², Wen Guo¹, Xunxia Bao¹, Dandan Wang¹, Baihui Ren¹, Haifeng Wang², Yu Li², Yueyue Wang², Sulian Chen³, Baoding Tang⁴, Qingling Yang^3,* and Changjie Chen^3,*

¹ Department of Biotechnology, Bengbu Medical College, Anhui, Bengbu 233030, China

² Clinical Testing and Diagnose Experimental Center, Bengbu Medical College, Anhui, Bengbu 233030, China

³ Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui, Bengbu 233030, China

⁴ Department of Oncology, Bengbu Medical College, Anhui, Bengbu 233030, China

Molecules 2017, 22(11), 1814; https://doi.org/10.3390/molecules22111814 - 25 Oct 2017

Cited by 115 | Viewed by 7028

Abstract

In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the [...] Read more.

In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using emulsification and low-temperature solidification method. The Res-SLNs were spherical, with small size, negative charge, and narrow size distribution. Compared with free resveratrol, the Res-SLNs displayed a superior ability in inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells. Western blot analysis revealed that Res-SLNs could promote the ratio of Bax/Bcl-2 but decreased the expression of cyclinD1 and c-Myc. These results indicate that the Res-SLN may have great potential for breast cancer treatment. Full article

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20 pages, 4059 KiB

Open AccessArticle

Studies on the Synthesis, Photophysical and Biological Evaluation of Some Unsymmetrical Meso-Tetrasubstituted Phenyl Porphyrins

by Rica Boscencu¹, Gina Manda^2,*

, Natalia Radulea^1,*, Radu Petre Socoteanu^3,*, Laura Cristina Ceafalan², Ionela Victoria Neagoe², Isabel Ferreira Machado^4,5

, Selma Huveyda Basaga^6,7 and Luís Filipe Vieira Ferreira⁴

¹ Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia St., 020956 Bucharest, Romania

² “Victor Babeş” National Institute of Pathology, 99-101 Splaiul Independentei, 050096 Bucharest, Romania

³ “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Splaiul Independentei, 060021 Bucharest, Romania

⁴ Centro de Química-Física Molecular, Institute of Nanosciences and Nanotechnology, Instituto Superior Técnico Av. Rovisco Pais 1049-001, Lisboa, Portugal

⁵ Polytechnic Institute of Portalegre, P-7300-110 Portalegre, Portugal

⁶ Dokumar, Teknopark Blvd No 1 Pendik 34906, Istanbul, Turkey

⁷ Molecular Biology Genetics & Bioengineering Program, Faculty of Engineering & Natural Sciences, Sabanci University, Orhanli 34956 Tuzla, Istanbul, Turkey

Molecules 2017, 22(11), 1815; https://doi.org/10.3390/molecules22111815 - 25 Oct 2017

Cited by 22 | Viewed by 5744

Abstract

Abstract: We designed three unsymmetrical meso-tetrasubstituted phenyl porphyrins for further development as theranostic agents for cancer photodynamic therapy (PDT): 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (P2.2), Zn(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Zn(II)2.2) and Cu(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Cu(II)2.2). The porphyrinic compounds were synthesized and their structures were confirmed by elemental analysis, FT-IR, UV-Vis, EPR [...] Read more.

Abstract: We designed three unsymmetrical meso-tetrasubstituted phenyl porphyrins for further development as theranostic agents for cancer photodynamic therapy (PDT): 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (P2.2), Zn(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Zn(II)2.2) and Cu(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Cu(II)2.2). The porphyrinic compounds were synthesized and their structures were confirmed by elemental analysis, FT-IR, UV-Vis, EPR and NMR. The compounds had a good solubility in polar/nonpolar media. P2.2 and, to a lesser extent, Zn(II)2.2 were fluorescent, albeit with low fluoresence quantum yields. P2.2 and Zn(II)2.2 exhibited PDT-acceptable values of singlet oxygen generation. A “dark” cytotoxicity study was performed using cells that are relevant for the tumor niche (HT-29 colon carcinoma cells and L929 fibroblasts) and for blood (peripheral mononuclear cells). Cellular uptake of fluorescent compounds, cell viability/proliferation and death were evaluated. P2.2 was highlighted as a promising theranostic agent for PDT in solid tumors considering that P2.2 generated PDT-acceptable singlet oxygen yields, accumulated into tumor cells and less in blood cells, exhibited good fluorescence within cells for imagistic detection, and had no significant cytotoxicity in vitro against tumor and normal cells. Complexing of P2.2 with Zn(II) or Cu(II) altered several of its PDT-relevant properties. These are consistent arguments for further developing P2.2 in animal models of solid tumors for in vivo PDT. 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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12 pages, 2152 KiB

Open AccessArticle

Synthesis, Crystal Structure, and Photoluminescent Properties of 3,3′,4,4′-Tetraethyl-5,5′-divinyl-2,2′-bipyrrole Derivatives

by Toru Okawara^1,*, Reo Kawano², Hiroya Morita², Alan Finkelstein³, Renjiro Toyofuku⁴, Kanako Matsumoto⁴, Kenji Takehara¹, Toshihiko Nagamura¹, Seiji Iwasa⁵ and Sanjai Kumar^3,6

¹ Department of Creative Engineering, National Institute of Technology, Kitakyushu College, 5-20-1 Shi-i, Kokuraminami-ku, Kitakyushu 802-0985, Japan

² Advanced School of Creative Engineering, National Institute of Technology, Kitakyushu College, 5-20-1 Shi-i, Kokuraminami-ku, Kitakyushu 802-0985, Japan

³ Department of Chemistry and Biochemistry, Queens College, Queens, NY 11367, USA

⁴ Department of Materials Science and Chemical Engineering, National Institute of Technology, Kitakyushu College, 5-20-1 Shi-i, Kokuraminami-ku, Kitakyushu 802-0985, Japan

⁵ Department of Environmental and Life Sciences, Toyohashi University of Technology, 1-1 Tempaku-cho, Toyohashi, Aichi 441-8580, Japan

⁶ Ph.D. Program in Chemistry and Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA

Molecules 2017, 22(11), 1816; https://doi.org/10.3390/molecules22111816 - 26 Oct 2017

Cited by 5 | Viewed by 5386

Abstract

Photoluminescent divinylbipyrroles were synthesized from 3,3′,4,4′-tetraetyl-2,2′-bipyrrole-5,5′-dicarboxaldehyde and activated methylene compounds via aldol condensation. For mechanistic clarity, molecular structures of Meldrum’s acid- and 1,3-dimethylbarbituric acid-derived divinylbipyrroles were determined by single-crystal X-ray diffraction. Photoluminescent properties of the synthesized divinylbipyrroles in dichloromethane were found to be [...] Read more.

Photoluminescent divinylbipyrroles were synthesized from 3,3′,4,4′-tetraetyl-2,2′-bipyrrole-5,5′-dicarboxaldehyde and activated methylene compounds via aldol condensation. For mechanistic clarity, molecular structures of Meldrum’s acid- and 1,3-dimethylbarbituric acid-derived divinylbipyrroles were determined by single-crystal X-ray diffraction. Photoluminescent properties of the synthesized divinylbipyrroles in dichloromethane were found to be dependent on the presence of electron withdrawing groups at the vinylic terminal. The divinylbipyrroles derived from malononitrile, Meldrum’s acid, and 1,3-dimethylbarbituric acid showed fluorescent peaks at 553, 576, and 602 nm respectively. Computational studies indicated that the alkyl substituents on the bipyrrole 3 and 3′ positions increased energy level of the highest occupied molecular orbital (HOMO) compared to the unsubstituted derivatives and provided rationale for the bathochromic shift of the ultraviolet-visible (UV-Vis) spectra compared to the previously reported analogs. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 1756 KiB

Open AccessArticle

Tryptophan-Containing Cyclic Decapeptides with Activity against Plant Pathogenic Bacteria

by Cristina Camó¹, Maria Torné¹, Emili Besalú²

, Cristina Rosés¹, Anna D. Cirac¹, Gemma Moiset¹, Esther Badosa³, Eduard Bardají^1,*, Emilio Montesinos^3,*

, Marta Planas^1,*

and Lidia Feliu^1,*

¹ LIPPSO, Departament de Química, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain

² Institut de Química Computacional i Catàlisi i Departament de Química, University of Girona, Maria Aurèlia Capmany 69, 17003 Girona, Spain

³ Laboratory of Plant Pathology, Institute of Food and Agricultural Technology-CIDSAV-XaRTA, University of Girona, Maria Aurèlia Capmany 61, 17003 Girona, Spain

Molecules 2017, 22(11), 1817; https://doi.org/10.3390/molecules22111817 - 26 Oct 2017

Cited by 9 | Viewed by 4448

Abstract

A library of 66 cyclic decapeptides incorporating a Trp residue was synthesized on solid phase and screened against the phytopathogenic bacteria Pseudomonas syringae pv. syringae, Xanthomonas axonopodis pv. vesicatoria, and Erwinia amylovora. The hemolytic activity of these peptides was also evaluated. [...] Read more.

A library of 66 cyclic decapeptides incorporating a Trp residue was synthesized on solid phase and screened against the phytopathogenic bacteria Pseudomonas syringae pv. syringae, Xanthomonas axonopodis pv. vesicatoria, and Erwinia amylovora. The hemolytic activity of these peptides was also evaluated. The results obtained were compared with those of a collection of Phe analogues previously reported. The analysis of the data showed that the presence of the Trp improved the antibacterial activity against these three pathogens. In particular, 40 to 46 Trp analogues displayed lower minimum inhibitory concentration (MIC) values than their corresponding Phe counterparts. Interestingly, 26 Trp-containing sequences exhibited MIC of 0.8 to 3.1 μM against X. axonopodis pv. vesicatoria, 21 peptides MIC of 1.6 to 6.2 μM against P. syringae pv. syringae and six peptides MIC of 6.2 to 12.5 μM against E. amylovora. Regarding the hemolysis, in general, Trp derivatives displayed a percentage of hemolysis comparable to that of their Phe analogues. Notably, 49 Trp-containing cyclic peptides showed a hemolysis ≤ 20% at 125 μM. The peptides with the best biological activity profile were c(LKKKLWKKLQ) (BPC086W) and c(LKKKKWLLKQ) (BPC108W), which displayed MIC values ranging from 0.8 to 12.5 μM and a hemolysis ≤ 8% at 125 μM. Therefore, it is evident that these Trp sequences constitute promising candidates for the development of new agents for use in plant protection. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Peptidomimetics)

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17 pages, 1771 KiB

Open AccessReview

How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound Repair

by Peter Gál^1,2,3,*

, Lenka Varinská^1,2, Lenka Fáber², Štepán Novák^4,5, Pavol Szabo^1,4,6, Petra Mitrengová³, Andrej Mirossay², Pavel Mučaji^3,* and Karel Smetana^4,6

¹ Department for Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., 040 11 Košice, Slovakia

² Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 11 Košice, Slovakia

³ Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia

⁴ Institute of Anatomy, 1st Faculty of Medicine, Charles University, 128 00 Prague, Czech Republic

⁵ Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University and University Hospital Motol, 150 06 Prague, Czech Republic

⁶ BIOCEV, 252 50 Vestec, Czech Republic

Molecules 2017, 22(11), 1818; https://doi.org/10.3390/molecules22111818 - 26 Oct 2017

Cited by 52 | Viewed by 8577

Abstract

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive [...] Read more.

It is now suggested that the inhibition of biological programs that are associated with the tumor microenvironment may be critical to the diagnostics, prevention and treatment of cancer. On the other hand, a suitable wound microenvironment would accelerate tissue repair and prevent extensive scar formation. In the present review paper, we define key signaling molecules (growth factors, cytokines, chemokines, and galectins) involved in the formation of the tumor microenvironment that decrease overall survival and increase drug resistance in cancer suffering patients. Additional attention will also be given to show whether targeted modulation of these regulators promote tissue regeneration and wound management. Whole-genome transcriptome profiling, in vitro and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X-C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix (e.g., fibronectin) do have similar regulation during wound healing and tumor growth. Published data demonstrate remarkable similarities between the tumor and wound microenvironments. Therefore, tailor made manipulation of cancer stroma can have important therapeutic consequences. Moreover, better understanding of cancer cell-stroma interaction can help to improve wound healing by supporting granulation tissue formation and process of reepithelization of extensive and chronic wounds as well as prevention of hypertrophic scars and formation of keloids. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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14 pages, 5115 KiB

Open AccessReview

Advances in Fluorescent Single-Chain Nanoparticles

by Julen De-La-Cuesta^1,2, Edurne González¹ and José A. Pomposo^1,2,3,*

¹ Centro de Física de Materiales (CSIC, UPV/EHU)—MPC, Materials Physics Center, Paseo Manuel de Lardizabal 5, E-20018 San Sebastian, Spain

² Departamento de Física de Materiales, Universidad del País Vasco (UPV/EHU), 1072 Apartado, E-20080 San Sebastian, Spain

³ IKERBASQUE—Basque Foundation for Science, María Díaz de Haro 3, E-48013 Bilbao, Spain

Molecules 2017, 22(11), 1819; https://doi.org/10.3390/molecules22111819 - 26 Oct 2017

Cited by 38 | Viewed by 6440

Abstract

Fluorophore molecules can be monitored by fluorescence spectroscopy and microscopy, which are highly useful and widely used techniques in cell biology, biochemistry, and medicine (e.g., biomarker analysis, immunoassays, cancer diagnosis). Several fluorescent micro- and nanoparticle systems based on block copolymer micelles and cross-linked [...] Read more.

Fluorophore molecules can be monitored by fluorescence spectroscopy and microscopy, which are highly useful and widely used techniques in cell biology, biochemistry, and medicine (e.g., biomarker analysis, immunoassays, cancer diagnosis). Several fluorescent micro- and nanoparticle systems based on block copolymer micelles and cross-linked polymer networks, quantum dots, π-conjugated polymers, and dendrimers have been evaluated as optical imaging systems. In this review, we highlight recent advances in the construction of fluorescent single-chain nanoparticles (SCNPs), which are valuable artificial soft nano-objects with a small tunable size (as small as 3 nm). In particular, the main methods currently available to endow SCNPs with fluorescent properties are discussed in detail, showing illustrative examples. Full article

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15 pages, 893 KiB

Open AccessArticle

Synthesis and 2D-QSAR Study of Active Benzofuran-Based Vasodilators

by Nagy M. Khalifa^1,2

, Aladdin M. Srour^2,*,†, Somaia S. Abd El-Karim^2,†, Dalia O. Saleh^3,† and Mohamed A. Al-Omar¹

¹ Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

² Therapeutical Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt

³ Pharmacology Department, National Research Centre, Dokki, Giza 12622, Egypt

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1820; https://doi.org/10.3390/molecules22111820 - 26 Oct 2017

Cited by 17 | Viewed by 5416

Abstract

A new series of 2-alkyloxy-pyridine-3-carbonitrile-benzofuran hybrids (4a–x) was synthesized. All the new derivatives were examined via the standard technique for their vasodilation activity. Some of the investigated compounds exhibited a remarkable activity, with compounds 4w, 4e, 4r [...] Read more.

A new series of 2-alkyloxy-pyridine-3-carbonitrile-benzofuran hybrids (4a–x) was synthesized. All the new derivatives were examined via the standard technique for their vasodilation activity. Some of the investigated compounds exhibited a remarkable activity, with compounds 4w, 4e, 4r, 4s, 4f and 4g believed to be the most active hits in this study with IC₅₀ values 0.223, 0.253, 0.254, 0.268, 0.267 and 0.275 mM, respectively, compared with amiodarone hydrochloride, the reference standard used (IC50 = 0.300 mM). CODESSA PRO was employed to obtain a statistically significant 2-Dimensional Quantitative Structure Activity Relationship (2D-QSAR) model describing the bioactivity of the newly synthesized analogs (N = 24, n = 4, R² = 0.816, R²_cvOO = 0.731, R²_cvMO = 0.772, F = 21.103, s² = 6.191 × 10⁻⁸). Full article

(This article belongs to the Section Bioorganic Chemistry)

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6 pages, 743 KiB

Open AccessEditorial

Atomic Sulfur: An Element for Adaptation to an Oxidative Environment

by Noryuki Nagahara^1,* and Maria Wróbel^2,*

¹ Isotope Research Center, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602 Tokyo, Japan

² Chair of Medical Biochemistry, Kopernika 7 St., Jagiellonian University Medical College, 31-034 Kraków, Poland

Molecules 2017, 22(11), 1821; https://doi.org/10.3390/molecules22111821 - 26 Oct 2017

Cited by 3 | Viewed by 4251

Abstract

During the period of rising oxygen concentration in the Earth’s atmosphere (Figure 1), sulfur atoms were incorporated into proteins as redox-active cysteine residues [1] and antioxidant molecules such as thioredoxin, glutathione, and glutaredoxin appeared [...]
Full article

(This article belongs to the Special Issue Sulfur Atom: Element for Adaptation to an Oxidative Environment 2016)

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12 pages, 4636 KiB

Open AccessArticle

The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

by Liyan Ji^1,2,3

, Xi Liu¹, Shuwei Zhang¹, Shunan Tang³, Simin Yang³, Shasha Li³, Xiaoxiao Qi¹, Siwang Yu³, Linlin Lu¹, Xiangbao Meng^3,*

and Zhongqiu Liu^1,*

¹ International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

² The Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

³ Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Molecules 2017, 22(11), 1822; https://doi.org/10.3390/molecules22111822 - 26 Oct 2017

Cited by 21 | Viewed by 6042

Abstract

Multidrug resistance (MDR) is a major cause of the inefficacy and poor response to paclitaxel-based chemotherapy. The combination of conventional cytotoxic drugs has been a plausible strategy for overcoming paclitaxel resistance. Herein, we investigated the cytotoxic effects and underlying mechanism of LSS-11, [...] Read more.

Multidrug resistance (MDR) is a major cause of the inefficacy and poor response to paclitaxel-based chemotherapy. The combination of conventional cytotoxic drugs has been a plausible strategy for overcoming paclitaxel resistance. Herein, we investigated the cytotoxic effects and underlying mechanism of LSS-11, a novel naphthalimide derivative-based topoisomerase inhibitor, in paclitaxel-resistant A549 (A549/T) lung cancer cells. LSS-11 enhanced cell death in A549/T cells by inducing apoptosis through increasing the DR5 protein level and PARP1 cleavage. Importantly, LSS-11 dose-dependently reduced STAT3 phosphorylation and downregulated its target genes MDR1 and MRP1, without affecting P-gp transport function. Chromatin coimmunoprecipitation (ChIP) assay further revealed that LSS-11 hindered the binding of STAT3 to the MDR1 and MRP1 promoters. Additionally, pharmacological inhibition of p-STAT3 by sulforaphane downregulated MDR1 and MRP1, resulting in A549/T cell death by triggering apoptosis. Collectively, our data show that LSS-11 is a potent naphthalimide-based chemosensitizer that could enhance cell death in paclitaxel-resistant lung cancer cells through the DR5/PARP1 pathway and STAT3/MDR1/MRP1 STAT3 inhibition. Full article

(This article belongs to the Section Medicinal Chemistry)

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14 pages, 1842 KiB

Open AccessArticle

Asperflavin, an Anti-Inflammatory Compound Produced by a Marine-Derived Fungus, Eurotium amstelodami

by Xiudong Yang^1,2, Min-Cheol Kang², Yong Li³, Eun-A. Kim², Sung-Myung Kang⁴ and You-Jin Jeon^2,5,*

¹ College of Chemical and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China

² Department of Marine Life Science, Jeju National University, Jeju 690-756, Korea

³ College of Pharmacy Science, Changchun University of Traditional Chinese Medicine, Changchun 130017, China

⁴ Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Calgary, AB T2N1N4, Canada

⁵ Marine and Environmental Research Institute, Jeju National University, Jeju 695-814, Korea

Molecules 2017, 22(11), 1823; https://doi.org/10.3390/molecules22111823 - 29 Oct 2017

Cited by 26 | Viewed by 5684

Abstract

In the present study, 16 marine-derived fungi were isolated from four types of marine materials including float, algae, animals and drift woods along with the coast of Jeju Island, Korea and evaluated for anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 24.7 cells. The broth [...] Read more.

In the present study, 16 marine-derived fungi were isolated from four types of marine materials including float, algae, animals and drift woods along with the coast of Jeju Island, Korea and evaluated for anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW 24.7 cells. The broth and mycelium extracts from the 16 fungi were prepared and the broth extract (BE) of Eurotium amstelodami (015-2) inhibited nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells without cytotoxicity. By further bioassay-guided isolation, three compounds including asperflavin, neoechinulin A and preechinulin were successfully isolated from the BE of E. amstelodami. It was revealed that asperflavin showed no cytotoxicity up to 200 μM and significantly inhibited LPS-induced NO and PGE2 production in a dose-dependent manner. In the western blot results, asperflavin suppressed only inducible NOS (iNOS), but COX-2 were slightly down-regulated. Asperflavin was also observed to inhibit the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. In conclusion, this study reports a potential use of asperflavin isolated from a marine fungus, E. amstelodami as an anti-inflammatory agent via suppression of iNOS and pro-inflammatory cytokines as well as no cytotoxicity. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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12 pages, 1815 KiB

Open AccessArticle

Acrylated Composite Hydrogel Preparation and Adsorption Kinetics of Methylene Blue

by Jinpeng Wang^1,2,3,*, Xiaobing Meng^1,2,3, Zheng Yuan^1,2,3, Yaoqi Tian^1,3, Yuxiang Bai^1,3 and Zhengyu Jin^1,2,3

¹ State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China

² School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China

³ Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, Wuxi 214122, Jiangsu, China

Molecules 2017, 22(11), 1824; https://doi.org/10.3390/molecules22111824 - 26 Oct 2017

Cited by 19 | Viewed by 4678

Abstract

By using cyclodextrin (α-CD) self-assembly into a hydrogel with the triblock copolymer Pluronic F127, nanomicrocrystalline cellulose was introduced into a gel system to form a composite CNC-β-CD/α-CD/Pluronic F127 hydrogel (CCH). CCH was modified further by grafting acrylic acid to form a novel acrylated [...] Read more.

By using cyclodextrin (α-CD) self-assembly into a hydrogel with the triblock copolymer Pluronic F127, nanomicrocrystalline cellulose was introduced into a gel system to form a composite CNC-β-CD/α-CD/Pluronic F127 hydrogel (CCH). CCH was modified further by grafting acrylic acid to form a novel acrylated composite hydrogel (ACH). The swelling degree of ACH was 156 g/g. Adsorption isotherms show that the adsorption process for methylene blue proximity fitted the Freundlich model. The adsorption kinetics showed that ACH followed a quasi-second-order kinetic model. Methylene blue desorption showed that ACH was a temperature- and pH-dependent gel. Repeated adsorption and desorption experiments were carried out three times, and the removal rate of methylene blue at 75 mg/L was still 70.1%. Full article

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9 pages, 835 KiB

Open AccessArticle

Chemical Constituents from the Flower of Hosta plantaginea with Cyclooxygenases Inhibition and Antioxidant Activities and Their Chemotaxonomic Significance

by Li Yang¹, Shu-Tai Jiang², Qin-Guang Zhou³, Guo-Yue Zhong³ and Jun-Wei He^3,*

¹ Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Ministry of Education, Nanchang 330004, China

² Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China

³ Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China

Molecules 2017, 22(11), 1825; https://doi.org/10.3390/molecules22111825 - 26 Oct 2017

Cited by 44 | Viewed by 4151

Abstract

Two new phenolic glucosides, hostaflavanone A (1) and anti-1-phenylpropane-1,2-diol-2-O-β-d-glucopyranoside (2), together with six known compounds, anti-1-phenylpropane-1,2-diol (3), phenethyl-O-β-d-glucopyranoside (4), phenethanol-β-d-gentiobioside (5), [...] Read more.

Two new phenolic glucosides, hostaflavanone A (1) and anti-1-phenylpropane-1,2-diol-2-O-β-d-glucopyranoside (2), together with six known compounds, anti-1-phenylpropane-1,2-diol (3), phenethyl-O-β-d-glucopyranoside (4), phenethanol-β-d-gentiobioside (5), phenethyl-O-rutinoside (6), (1S, 3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (7), and (1R, 3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (8), were isolated from the flower of Hosta plantaginea, and their structures were elucidated by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), and circular dichroism (CD) analyses. The cyclooxygenases (COX-1 and COX-2) inhibition and antioxidant activities of compounds 1 and 4–6 were investigated, and they showed moderate cyclooxygenases inhibition activities. Moreover, only compound 1 exhibited moderate antioxidant activity, with an IC₅₀ value of 83.2 μM, while 4–6 showed insignificant activity with IC₅₀ values of 282, 257, and 275 μM, respectively. This is the first report of compounds 3 and 5–8 from the Liliaceae family. The chemotaxonomic significance of the isolated compounds was also summarized. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 1913 KiB

Open AccessArticle

Spectrum-Effect Relationships between Fingerprints of Caulophyllum robustum Maxim and Inhabited Pro-Inflammation Cytokine Effects

by Shaowa Lü¹, Shuyu Dong¹, Dan Xu¹, Jixin Duan¹, Guoyu Li², Yuyan Guo¹, Haixue Kuang^1,* and Qiuhong Wang^1,3,*

¹ Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China

² Pharmaceutical College, Harbin University of Commerce, Harbin 150086, China

³ Pharmaceutical College, Guangdong Pharmaceutical University, Guangzhou 510224, China

Molecules 2017, 22(11), 1826; https://doi.org/10.3390/molecules22111826 - 26 Oct 2017

Cited by 25 | Viewed by 5230

Abstract

Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were [...] Read more.

Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were detected by fingerprint similarity evaluation software. Among them, 15 peaks were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen-induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different batches of CRM with four pro-inflammation cytokines (TNF-α, IL-β, IL-6, and IL-17) as indicators. These cytokines were suppressed at different levels according to the different batches of CRM treatment. The spectrum-effect relationships between chemical fingerprints and the pro-inflammation effects of CRM were established by multiple linear regression (MLR) and gray relational analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (N-methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D, leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic acid), β-sitosterols, and unknown compounds (X3, X17) together showed anti-inflammatory efficacy. The results also showed that the correlation between saponins and inflammatory factors was significantly closer than that of alkaloids, and saponins linked with less sugar may have higher inhibition effect on pro-inflammatory cytokines in CIA mice. This work provided a general model of the combination of HPLC and anti-inflammatory effects to study the spectrum-effect relationships of CRM, which can be used to discover the active substance and to control the quality of this treatment. Full article

(This article belongs to the Collection Herbal Medicine Research)

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18 pages, 3319 KiB

Open AccessArticle

New 2-Phenylthiazoles as Potential Sortase A Inhibitors: Synthesis, Biological Evaluation and Molecular Docking

by Smaranda Dafina Oniga^1,†

, Cătălin Araniciu^1,*,†

, Mariana Doina Palage^1,*

, Marcela Popa^2,3, Mariana-Carmen Chifiriuc^2,3

, Gabriel Marc¹

, Adrian Pirnau⁴, Cristina Ioana Stoica¹, Ioannis Lagoudis¹

, Theodoros Dragoumis¹

and Ovidiu Oniga¹

¹ Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 8 Victor Babes St, 400012 Cluj-Napoca, Romania

² Department of Microbiology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Street, 60101 Bucharest, Romania

³ Research Institute of the University of Bucharest-ICUB, 91-95 Independentei Street, 050095 Bucharest, Romania

⁴ National Institute for Research and Development of Isotopic and Molecular Technologies, 67-103 Donat Street, 400293 Cluj-Napoca, Romania

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1827; https://doi.org/10.3390/molecules22111827 - 27 Oct 2017

Cited by 29 | Viewed by 6239

Abstract

Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act [...] Read more.

Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act as Sortase A inhibitors provided the starting point for identifying a new potential scaffold. Based on this template a series of new potential Sortase A inhibitors, that contain the 2-phenylthiazole moiety, were synthesized. The physicochemical characterisation confirmed the identity of the proposed structures. Antibacterial activity evaluation showed that the new compounds have a reduced activity against bacterial cell viability. However, the compounds prevent biofilm formation at very low concentrations, especially in the case of E. faecalis. Molecular docking studies performed estimate that this is most likely due to the inhibition of Sortase A. The new compounds could be used as add-on therapies together with known antibacterial agents in order to combat multidrug-resistance enterococcal infections. Full article

(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)

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16 pages, 3474 KiB

Open AccessArticle

Bacterial Expression of Human Butyrylcholinesterase as a Tool for Nerve Agent Bioscavengers Development

by Xavier Brazzolotto^1,*

, Alexandre Igert¹, Virginia Guillon¹, Gianluca Santoni²

and Florian Nachon¹

¹ Institut de Recherche Biomédicale des Armées, Département de Toxicologie et Risques Chimiques, 1 Place Général Valérie André, 91223 Brétigny-sur-Orge, France

² European Synchrotron Radiation Facility, 71 Avenue des Martyrs, 38043 Grenoble CEDEX 9, France

Molecules 2017, 22(11), 1828; https://doi.org/10.3390/molecules22111828 - 27 Oct 2017

Cited by 30 | Viewed by 6490

Abstract

Human butyrylcholinesterase is a performant stoichiometric bioscavenger of organophosphorous nerve agents. It is either isolated from outdated plasma or functionally expressed in eukaryotic systems. Here, we report the production of active human butyrylcholinesterase in a prokaryotic system after optimization of the primary sequence [...] Read more.

Human butyrylcholinesterase is a performant stoichiometric bioscavenger of organophosphorous nerve agents. It is either isolated from outdated plasma or functionally expressed in eukaryotic systems. Here, we report the production of active human butyrylcholinesterase in a prokaryotic system after optimization of the primary sequence through the Protein Repair One Stop Shop process, a structure- and sequence-based algorithm for soluble bacterial expression of difficult eukaryotic proteins. The mutant enzyme was purified to homogeneity. Its kinetic parameters with substrate are similar to the endogenous human butyrylcholinesterase or recombinants produced in eukaryotic systems. The isolated protein was prone to crystallize and its 2.5-Å X-ray structure revealed an active site gorge region identical to that of previously solved structures. The advantages of this alternate expression system, particularly for the generation of butyrylcholinesterase variants with nerve agent hydrolysis activity, are discussed. Full article

(This article belongs to the Special Issue The Cholinesterases—Structure, Mechanism, Function and Drug Design: The 25th Anniversary of the Solution of the Crystal Structure of Acetylcholinesterase by Joel L. Sussman and Israel Silman)

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12 pages, 2303 KiB

Open AccessArticle

Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources

by Yosuke Matsubara^1,*, Takashi Matsumoto¹

, Junichi Koseki¹, Atsushi Kaneko¹, Setsuya Aiba² and Kenshi Yamasaki²

¹ Tsumura Research Laboratories, Tsumura & Co., Ibaraki 300-1192, Japan

² Department of Dermatology, Tohoku University Graduate School of Medicine, Miyagi 980-8574, Japan

Molecules 2017, 22(11), 1829; https://doi.org/10.3390/molecules22111829 - 27 Oct 2017

Cited by 16 | Viewed by 7326

Abstract

Stratum corneum tryptic enzyme kallikrein 5 (KLK5) is a serine protease that is involved in the cell renewal and maintenance of the skin barrier function. The excessive activation of KLK5 causes an exacerbation of dermatoses, such as rosacea and atopic dermatitis. Some triterpenoids [...] Read more.

Stratum corneum tryptic enzyme kallikrein 5 (KLK5) is a serine protease that is involved in the cell renewal and maintenance of the skin barrier function. The excessive activation of KLK5 causes an exacerbation of dermatoses, such as rosacea and atopic dermatitis. Some triterpenoids are reported to suppress the serine proteases. We aimed to investigate whether bioactive triterpenoids modulate the KLK5 protease. Nineteen triterpenoids occurring in medicinal crude drugs were evaluated using an enzymatic assay to measure the anti-KLK5 activity. The KLK5-dependent cathelicidin peptide LL-37 production in human keratinocytes was examined using immunoprecipitation and Western blotting. Screening assays for evaluating the anti-KLK5 activity revealed that ursolic acid, oleanolic acid, saikosaponin b₁, tumulosic acid and pachymic acid suppressed the KLK5 protease activity, although critical molecular moieties contributing to anti-KLK5 activity were unclarified. Ursolic acid and tumulosic acid suppressed the proteolytic processing of LL-37 in keratinocytes at ≤10 μM; no cytotoxicity was observed. Both triterpenoids were detected in the plasma of rats administered orally with triterpenoid-rich crude drug Jumihaidokuto. Our study reveals that triterpenoids, such as ursolic acid and tumulosic acid, modulate the KLK5 protease activity and cathelicidin peptide production. Triterpenoids may affect the skin barrier function via the regulation of proteases. Full article

(This article belongs to the Special Issue Biological Activity of Secondary Metabolites)

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13 pages, 1792 KiB

Open AccessArticle

Stenotrophomonas maltophilia: A Gram-Negative Bacterium Useful for Transformations of Flavanone and Chalcone

by Edyta Kostrzewa-Susłow^1,*, Monika Dymarska¹, Urszula Guzik²

, Danuta Wojcieszyńska² and Tomasz Janeczko¹

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

² Department of Biochemistry, Faculty of Biology and Environmental Protection, University of Silesia in Katowice, Jagiellonska 28, 40-032 Katowice, Poland

Molecules 2017, 22(11), 1830; https://doi.org/10.3390/molecules22111830 - 27 Oct 2017

Cited by 16 | Viewed by 5167

Abstract

A group of flavones, isoflavones, flavanones, and chalcones was subjected to small-scale biotransformation studies with the Gram-negative Stenotrophomonas maltophilia KB2 strain in order to evaluate the capability of this strain to transform flavonoid compounds and to investigate the relationship between compound structure and [...] Read more.

A group of flavones, isoflavones, flavanones, and chalcones was subjected to small-scale biotransformation studies with the Gram-negative Stenotrophomonas maltophilia KB2 strain in order to evaluate the capability of this strain to transform flavonoid compounds and to investigate the relationship between compound structure and transformation type. The tested strain transformed flavanones and chalcones. The main type of transformation of compounds with a flavanone moiety was central heterocyclic C ring cleavage, leading to chalcone and dihydrochalcone structures, whereas chalcones underwent reduction to dihydrochalcones and cyclisation to a benzo-γ-pyrone moiety. Substrates with a C-2–C-3 double bond (flavones and isoflavones) were not transformed by Stenotrophomonas maltophilia KB2. Full article

(This article belongs to the Section Bioorganic Chemistry)

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8 pages, 5333 KiB

Open AccessArticle

Binding of Harmine Derivatives to DNA: A Spectroscopic Investigation

by Bruno Pagano¹

, Marco Caterino¹, Rosanna Filosa² and Concetta Giancola^1,*

¹ Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy

² Department of Experimental Medicine, Campania University “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy

Molecules 2017, 22(11), 1831; https://doi.org/10.3390/molecules22111831 - 27 Oct 2017

Cited by 15 | Viewed by 5919

Abstract

Harmine belongs to a group of β-carboline alkaloids endowed with antitumor properties. Harmine and its derivatives are thought to bind to DNA and interfere with topoisomerase activities. We investigated the base-dependent binding of harmine, and three of its synthetic anticancer-active derivatives to the [...] Read more.

Harmine belongs to a group of β-carboline alkaloids endowed with antitumor properties. Harmine and its derivatives are thought to bind to DNA and interfere with topoisomerase activities. We investigated the base-dependent binding of harmine, and three of its synthetic anticancer-active derivatives to the genomic DNA from calf thymus and two synthetic 20-mer double helices, the poly(dG-dC)·poly(dG-dC) and the poly(dA-dT)·poly(dA-dT), by means of UV-Vis and circular dichroism (CD) spectroscopies. The data show that the DNA binding and stabilising properties of the investigated derivatives are base pair-dependent. These results could be used as a guide to design and develop further bioactive analogues. Full article

(This article belongs to the Collection New Frontiers in Nucleic Acid Chemistry)

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14 pages, 734 KiB

Open AccessArticle

UPLC-PDA-Q/TOF-MS Profile of Polyphenolic Compounds of Liqueurs from Rose Petals (Rosa rugosa)

by Andrzej Cendrowski^1,*, Iwona Ścibisz¹, Marek Kieliszek^2,*

, Joanna Kolniak-Ostek³ and Marta Mitek¹

¹ Division of Fruit and Vegetable Technology, Department of Food Technology, Faculty of Food Sciences, Warsaw University of Life Sciences–SGGW, 159c Nowoursynowska Str., 02-776 Warsaw, Poland

² Division of Food Biotechnology and Microbiology, Department of Biotechnology, Microbiology and Food Evaluation, Faculty of Food Sciences, Warsaw University of Life Sciences—SGGW, 159c Nowoursynowska Str., 02-776 Warsaw, Poland

³ Department of Fruit, Vegetable and Nutraceutical Plant Technology, Faculty of Biotechnology and Food Science, Wroclaw University of Environmental and Life Sciences, 37/41 Chełmońskiego Str., 51-630 Wroclaw, Poland

Molecules 2017, 22(11), 1832; https://doi.org/10.3390/molecules22111832 - 27 Oct 2017

Cited by 39 | Viewed by 6162

Abstract

Polyphenolic compounds, as a secondary metabolite of plants, possess great nutritional and pharmacological potential. Herein, we applied the green analytical method to study the nutrient profile of Rosa rugosa petals and liqueurs manufactured from them. Using the fast and validated ultra performance liquid [...] Read more.

Polyphenolic compounds, as a secondary metabolite of plants, possess great nutritional and pharmacological potential. Herein, we applied the green analytical method to study the nutrient profile of Rosa rugosa petals and liqueurs manufactured from them. Using the fast and validated ultra performance liquid chromatography-photodiode detector-quadrupole/time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS) method, we confirm the presence of the following compounds: phenolic acids, flavonols, flavan-3-ols and hydrolisable tannins (gallotannins and ellagitannins). R. rugosa petals contains up to 2175.43 mg polyphenols per 100 g fresh weight, therein 1517.01 mg ellagitannins per 100 g fresh weight. Liqueurs, traditionally manufactured from said petals using a conventional extraction method (maceration), also contain polyphenols in significant amounts (from 72% to 96% corresponding to percentage of theoretical polyphenol content in the used petals), therein ellagitannins amount to 69.7% on average. We confirmed that traditional maceration, most common for the isolation of polyphenols, is still suitable for the food industry due to its using aqueous ethanol, a common bio-solvent, easily available in high purity and completely biodegradable. Therefore R. rugosa used as a food may be considered as an ellagitannin-rich plant of economic importance. Manufactured rose liqueurs were stable and kept all their properties during the whole period of aging. Full article

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28 pages, 3322 KiB

Open AccessReview

The Compounds Responsible for the Sensory Profile in Monovarietal Virgin Olive Oils

by Cristina Campestre^1,*

, Guido Angelini¹

, Carla Gasbarri¹

and Franca Angerosa²

¹ Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, via dei Vestini, 66100 Chieti, Italy

² Council for Agricultural Research and Economics (CREA), CREA-OLI Olive Growing and Oil Industry Research Centre, Viale Petruzzi 75, Città Sant’Angelo (PE) 65013, Italy

Molecules 2017, 22(11), 1833; https://doi.org/10.3390/molecules22111833 - 27 Oct 2017

Cited by 92 | Viewed by 8169

Abstract

Monovarietal virgin olive oils (VOOs) are very effective to study relationships among sensory attributes, the compounds responsible for flavour, and factors affecting them. The stimulation of the human sensory receptors by volatile and non-volatile compounds present in monovarietal virgin olive oils gives rise [...] Read more.

Monovarietal virgin olive oils (VOOs) are very effective to study relationships among sensory attributes, the compounds responsible for flavour, and factors affecting them. The stimulation of the human sensory receptors by volatile and non-volatile compounds present in monovarietal virgin olive oils gives rise to the sensory attributes that describe their peculiar delicate and fragrant flavours. The formation of these compounds is briefly illustrated and the influence of the agronomic and technological factors that affect their concentrations in the oil is examined. The relationships between compounds responsible for the olive oil flavour and sensory attributes are discussed. Several approaches for the varietal differentiation of monovarietal virgin olive oils are also overviewed. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1997 KiB

Open AccessArticle

‘Click Chemistry’ Synthesis of Novel Natural Product-Like Caged Xanthones Bearing a 1,2,3-Triazole Moiety with Improved Druglike Properties as Orally Active Antitumor Agents

by Xiang Li^1,2, Yue Wu^1,3, Yanyan Wang^1,3, Qidong You^1,3,* and Xiaojin Zhang^1,4,*

¹ Jiangsu Key Laboratory of Drug Design and Optimization, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

² Department of Pharmaceutical Engineering, China Pharmaceutical University, Nanjing 211198, China

³ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China

⁴ Department of Organic Chemistry, China Pharmaceutical University, Nanjing 211198, China

Molecules 2017, 22(11), 1834; https://doi.org/10.3390/molecules22111834 - 27 Oct 2017

Cited by 18 | Viewed by 5986

Abstract

DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of the Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro, but poor efficacy in vivo due to its poor druglike properties. In order to [...] Read more.

DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of the Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro, but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo antitumor potency, a novel series of ten triazole-bearing caged xanthone derivatives of DDO-6101 has been efficiently synthesized by ‘click chemistry’ and evaluated for their in vitro antitumor activity and druglike properties. Most of the target compounds have sustained cytotoxicity against A549, HepG2, HCT116, and U2OS cancer cells and possess improved aqueous solubility, as well as permeability. Notably, these caged xanthones are also active towards taxol-resistant or cisplatin-resistant A549 cancer cells. Taking both the in vitro activities and druglike properties into consideration, compound 8g has been advanced into in vivo efficacy experiments. The results reveal that 8g (named as DDO-6318), both by intravenous or per os administration, are much more potent than the lead DDO-6101 in A549-transplanted mice models and it could be a promising antitumor candidate for further evaluation. Full article

(This article belongs to the Collection Natural Products: Anticancer Potential and Beyond)

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8 pages, 1431 KiB

Open AccessArticle

Semisynthesis, an Anti-Inflammatory Effect of Derivatives of 1β-Hydroxy Alantolactone from Inula britannica

by Lin Chen^1,2, Jian-Ping Zhang³, Xin Liu², Jiang-Jiang Tang⁴, Ping Xiang^5,* and Xing-Ming Ma^1,*

¹ Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China

² Department of Infectious Disease, the First Hospital of Lanzhou University, Lanzhou 730000, China

³ Department of Pharmacy, the First Hospital of Lanzhou University, Lanzhou 730000, China

⁴ College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China

⁵ College of Plant Protection, Northwest A&F University, Yangling 712100, China

Molecules 2017, 22(11), 1835; https://doi.org/10.3390/molecules22111835 - 27 Oct 2017

Cited by 20 | Viewed by 5251

Abstract

1β-hydroxy alantolactone, a sesquiterpene lactone mainly isolated from Inula genus plants, exhibits potent anti-inflammatory and anticancer activities. In this work, 1β-hydroxy alantolactone was isolated and five derivatives were prepared through different reactions at the C1-OH and C13-methylene motifs. The structure–activity relationships (SAR) of [...] Read more.

1β-hydroxy alantolactone, a sesquiterpene lactone mainly isolated from Inula genus plants, exhibits potent anti-inflammatory and anticancer activities. In this work, 1β-hydroxy alantolactone was isolated and five derivatives were prepared through different reactions at the C1-OH and C13-methylene motifs. The structure–activity relationships (SAR) of anti-inflammatory effects against NO production in RAW264.7 cells showed that the α-methylene-γ-butyrolactone motif was essential for NO production suppression and that retaining the C1-OH group can remarkably improve this effect. The NF-κB signaling pathway plays a pivotal role in the regulation of NO expression. Moreover, the levels of p65 and p50 phosphorylation were investigated and active compound 1 inhibited phosphorylation of p65 and p50 in TNF-α-induced NF-κB signaling. Further molecular docking suggested that 1 may target the p65 of NF-κB. Full article

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11 pages, 2553 KiB

Open AccessArticle

Determination of the Bridging Ligand in the Active Site of Tyrosinase

by Congming Zou^1,†, Wei Huang^1,†, Gaokun Zhao¹, Xiao Wan², Xiaodong Hu¹, Yan Jin¹, Junying Li¹ and Junjun Liu^2,*

¹ Yunnan Academy of Tobacco Agricultural Sciences, 33 Yuantong Street, Kunming 650021, China

² School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China

^† These authors contribute equally to this work.

Molecules 2017, 22(11), 1836; https://doi.org/10.3390/molecules22111836 - 28 Oct 2017

Cited by 21 | Viewed by 6429

Abstract

Tyrosinase is a type-3 copper enzyme that is widely distributed in plants, fungi, insects, and mammals. Developing high potent inhibitors against tyrosinase is of great interest in diverse fields including tobacco curing, food processing, bio-insecticides development, cosmetic development, and human healthcare-related research. In [...] Read more.

Tyrosinase is a type-3 copper enzyme that is widely distributed in plants, fungi, insects, and mammals. Developing high potent inhibitors against tyrosinase is of great interest in diverse fields including tobacco curing, food processing, bio-insecticides development, cosmetic development, and human healthcare-related research. In the crystal structure of Agaricus bisporus mushroom tyrosinase, there is an oxygen atom bridging the two copper ions in the active site. It is unclear whether the identity of this bridging oxygen is a water molecule or a hydroxide anion. In the present study, we theoretically determine the identity of this critical bridging oxygen by performing first-principles hybrid quantum mechanics/molecular mechanics/Poisson-Boltzmann-surface area (QM/MM-PBSA) calculations along with a thermodynamic cycle that aim to improve the accuracy. Our results show that the binding with water molecule is energy favored and the QM/MM-optimized structure is very close to the crystal structure, whereas the binding with hydroxide anions causes the increase of energy and significant structural changes of the active site, indicating that the identity of the bridging oxygen must be a water molecule rather than a hydroxide anion. The different binding behavior between water and hydroxide anions may explain why molecules with a carboxyl group or too many negative charges have lower inhibitory activity. In light of this, the design of high potent active inhibitors against tyrosinase should satisfy both the affinity to the copper ions and the charge neutrality of the entire molecule. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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16 pages, 3964 KiB

Open AccessArticle

A Large Size Chimeric Highly Immunogenic Peptide Presents Multistage Plasmodium Antigens as a Vaccine Candidate System against Malaria

by José Manuel Lozano^1,*, Yahson Varela^1,2, Yolanda Silva², Karen Ardila^1,2, Martha Forero², Laura Guasca¹, Yuly Guerrero¹, Adriana Bermudez², Patricia Alba², Magnolia Vanegas² and Manuel Elkin Patarroyo^1,2

¹ Department of Pharmacy, Universidad Nacional de Colombia, Bogotá DC 111321, Colombia

² Fundación Instituto de Inmunología de Colombia (FIDIC)-Universidad del Rosario, Bogotá DC 111221, Colombia

Molecules 2017, 22(11), 1837; https://doi.org/10.3390/molecules22111837 - 1 Nov 2017

Cited by 4 | Viewed by 5093

Abstract

Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional [...] Read more.

Rational strategies for obtaining malaria vaccine candidates should include not only a proper selection of target antigens for antibody stimulation, but also a versatile molecular design based on ordering the right pieces from the complex pathogen molecular puzzle towards more active and functional immunogens. Classical Plasmodium falciparum antigens regarded as vaccine candidates have been selected as model targets in this study. Among all possibilities we have chosen epitopes of PfCSP, STARP; MSA1 and Pf155/RESA from pre- and erythrocyte stages respectively for designing a large 82-residue chimeric immunogen. A number of options aimed at diminishing steric hindrance for synthetic procedures were assessed based on standard Fmoc chemistry such as building block orthogonal ligation; pseudo-proline and microwave-assisted procedures, therefore the large-chimeric target was produced, characterized and immunologically tested. Antigenicity and functional in vivo efficacy tests of the large-chimera formulations administered alone or as antigen mixtures have proven the stimulation of high antibody titers, showing strong correlation with protection and parasite clearance of vaccinated BALB/c mice after being lethally challenged with both P. berghei-ANKA and P. yoelii 17XL malaria strains. Besides, 3D structure features shown by the large-chimera encouraged as to propose using these rational designed large synthetic molecules as reliable vaccine candidate-presenting systems. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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12 pages, 3157 KiB

Open AccessArticle

In-Silico UHPLC Method Optimization for Aglycones in the Herbal Laxatives Aloe barbadensis Mill., Cassia angustifolia Vahl Pods, Rhamnus frangula L. Bark, Rhamnus purshianus DC. Bark, and Rheum palmatum L. Roots

by Nadja Meier, Beat Meier, Samuel Peter and Evelyn Wolfram^*

Phytopharmacy & Natural Products Research Group, Institute of Chemistry and Biotechnology, Zuerich University of Applied Sciences (ZHAW), CH-8820 Waedenswil, Switzerland

Molecules 2017, 22(11), 1838; https://doi.org/10.3390/molecules22111838 - 27 Oct 2017

Cited by 16 | Viewed by 7427

Abstract

For the European Pharmacopoeia (Ph. Eur.) herbal monograph draft of Cassia angustifolia Vahl. and Cassia senna L. leaves and pods, a safety limitation of aloe-emodin and rhein was proposed, due to toxicological concerns. A quantitative, analytical method of the anthraquinone aglycones in all [...] Read more.

For the European Pharmacopoeia (Ph. Eur.) herbal monograph draft of Cassia angustifolia Vahl. and Cassia senna L. leaves and pods, a safety limitation of aloe-emodin and rhein was proposed, due to toxicological concerns. A quantitative, analytical method of the anthraquinone aglycones in all Ph. Eur. monographed herbal laxatives is of interest. A rational method development for the aglycones aloe-emodin, rhein, emodin, chrysophanol, and physcion in five herbal drugs was realized by using 3D chromatographic modelling (temperature, solvent, and gradient time) and design of experiment (DOE) software (DryLab^® 4). A methodical approach suitable for the challenging peak tracking in the chromatograms of the herbal drugs in dependence on the changes in the chromatographic conditions is described by using a combination of mass spectroscopy (MS) data (UHPLC-QDa), UV/Vis-spectra, and peak areas. The model results indicate a low robust range and showed that with the selected chromatographic system, small interferences could not be averted. The separation achieved shows a pure UV/Vis spectrum for all aglycones except for chrysophanol in Aloe barbadensis and emodin in Cassia angustifolia fruit. A gradient with the best resolution of the aglycones in all five drugs is proposed, and its suitability demonstrated for the quantification of aglycones in these herbal drugs. Full article

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

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16 pages, 2294 KiB

Open AccessArticle

Identification for the First Time of Cyclo(d-Pro-l-Leu) Produced by Bacillus amyloliquefaciens Y1 as a Nematocide for Control of Meloidogyne incognita

by Qaiser Jamal¹, Jeong-Yong Cho², Jae-Hak Moon³, Shahzad Munir⁴, Muhammad Anees⁵ and Kil Yong Kim^1,*

¹ Division of Food Technology, Biotechnology and Agro chemistry, Institute of Environmentally-Friendly Agriculture, Chonnam National University, Gwangju 61186, Korea

² Department of Food Science and Technology, and Functional Food Research Center, Chonnam National University, Gwangju 61186, Korea

³ Department of Food Science and Technology, BK21 Plus Program, Chonnam National University, Gwangju 61186, Korea

⁴ Faculty of Plant Protection, Yunnan Agricultural University, Kunming 650201, Yunnan, China

⁵ Department of Microbiology, Kohat University of Science and Technology, Kohat 26000, Pakistan

Molecules 2017, 22(11), 1839; https://doi.org/10.3390/molecules22111839 - 27 Oct 2017

Cited by 53 | Viewed by 6424

Abstract

The aim of the current study was to describe the role and mechanism of Bacillus amyloliquefaciens Y1 against the root-knot nematode, Meloidogyne incognita, under in vitro and in vivo conditions. Initially, the exposure of the bacterial culture supernatant and crude extract of Y1 [...] Read more.

The aim of the current study was to describe the role and mechanism of Bacillus amyloliquefaciens Y1 against the root-knot nematode, Meloidogyne incognita, under in vitro and in vivo conditions. Initially, the exposure of the bacterial culture supernatant and crude extract of Y1 to M. incognita significantly inhibited the hatching of eggs and caused the mortality of second-stage juveniles (J2), with these inhibitory effects depending on the length of incubation time and concentration of the treatment. The dipeptide cyclo(d-Pro-l-Leu) was identified in B. amyloliquefaciens culture for the first time using chromatographic techniques and nuclear magnetic resonance (NMR ¹H, ¹³C, H-H COSY, HSQC, and HMBC) and recognized to have nematocidal activity. Various concentrations of cyclo(d-Pro-l-Leu) were investigated for their effect on the hatching of eggs and J2 mortality. Moreover, the in vivo nematocidal activity of the Y1 strain was investigated by conducting pot experiments in which tomato plants were inoculated with M. incognita. Each and every pot was amended 50 mL of fertilizer media (F), or Y1 culture, or nematicide (N) (only once), or fertilizer media with N (FN) at 1, 2, 3, 4 and 5 weeks after transplantation. The results of the pot experiments demonstrated the antagonistic effect of B. amyloliquefaciens Y1 against M. incognita as it significantly decreases the count of eggs and galls per root of the tomato plant as well as the population of J2 in the soil. Besides, the investigation into the growth parameters, such as the length of shoot, shoot fresh and dry weights of the tomato plants, showed that they were significantly higher in the Y1 strain Y1-treated plants compared to F-, FN- and N-treated plants. Therefore, the biocontrol repertoire of this bacterium opens a new insight into the applications in crop pest control. Full article

(This article belongs to the Collection Bioactive Compounds)

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13 pages, 1668 KiB

Open AccessArticle

Design of Tail-Clamp Peptide Nucleic Acid Tethered with Azobenzene Linker for Sequence-Specific Detection of Homopurine DNA

by Shinjiro Sawada¹, Toshifumi Takao², Nobuo Kato¹ and Kunihiro Kaihatsu^1,*

¹ Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan

² Laboratory of Protein Profiling and Functional Proteomics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Molecules 2017, 22(11), 1840; https://doi.org/10.3390/molecules22111840 - 27 Oct 2017

Cited by 6 | Viewed by 6268

Abstract

DNA carries genetic information in its sequence of bases. Synthetic oligonucleotides that can sequence-specifically recognize a target gene sequence are a useful tool for regulating gene expression or detecting target genes. Among the many synthetic oligonucleotides, tail-clamp peptide nucleic acid (TC-PNA) offers advantages [...] Read more.

DNA carries genetic information in its sequence of bases. Synthetic oligonucleotides that can sequence-specifically recognize a target gene sequence are a useful tool for regulating gene expression or detecting target genes. Among the many synthetic oligonucleotides, tail-clamp peptide nucleic acid (TC-PNA) offers advantages since it has two homopyrimidine PNA strands connected via a flexible ethylene glycol-type linker that can recognize complementary homopurine sequences via Watson-Crick and Hoogsteen base pairings and form thermally-stable PNA/PNA/DNA triplex structures. Here, we synthesized a series of TC-PNAs that can possess different lengths of azobenzene-containing linkers and studied their binding behaviours to homopurine single-stranded DNA. Introduction of azobenzene at the N-terminus amine of PNA increased the thermal stability of PNA-DNA duplexes. Further extension of the homopyrimidine PNA strand at the N-terminus of PNA-AZO further increased the binding stability of the PNA/DNA/PNA triplex to the target homopurine sequence; however, it induced TC-PNA/DNA/TC-PNA complex formation. Among these TC-PNAs, 9W5H-C4-AZO consisting of nine Watson-Crick bases and five Hoogsteen bases tethered with a beta-alanine conjugated azobenzene linker gave a stable 1:1 TC-PNA/ssDNA complex and exhibited good mismatch recognition. Our design for TC-PNA-AZO can be utilized for detecting homopurine sequences in various genes. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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16 pages, 3529 KiB

Open AccessArticle

Herbicidal Activities of Some Allelochemicals and Their Synergistic Behaviors toward Amaranthus tricolor L.

by Nawasit Chotsaeng^1,*

, Chamroon Laosinwattana² and Patchanee Charoenying¹

¹ Department of Chemistry, Faculty of Science, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand

² Department of Plant Production Technology, Faculty of Agricultural Technology, King Mongkut’s Institute of Technology Ladkrabang, Bangkok 10520, Thailand

Molecules 2017, 22(11), 1841; https://doi.org/10.3390/molecules22111841 - 27 Oct 2017

Cited by 51 | Viewed by 6542

Abstract

Seven allelochemicals, namely R-(+)-limonene (A), vanillin (B), xanthoxyline (C), vanillic acid (D), linoleic acid (E), methyl linoleate (F), and (±)-odorine (G), were investigated for their herbicidal activities on [...] Read more.

Seven allelochemicals, namely R-(+)-limonene (A), vanillin (B), xanthoxyline (C), vanillic acid (D), linoleic acid (E), methyl linoleate (F), and (±)-odorine (G), were investigated for their herbicidal activities on Chinese amaranth (Amaranthus tricolor L.). At 400 μM, xanthoxyline (C) showed the greatest inhibitory activity on seed germination and seedling growth of the tested plant. Both vanillic acid (D) and (±)-odorine (G) inhibited shoot growth, however, apart from xanthoxyline (C), only vanillic acid (D) could inhibit root growth. Interestingly, R-(+)-limonene (A) lightly promoted root length. Other substances had no allelopathic effect on seed germination and seedling growth of the tested plant. To better understand and optimize the inhibitory effects of these natural herbicides, 21 samples of binary mixtures of these seven compounds were tested at 400 μM using 0.25% (v/v) Tween^® 80 as a control treatment. The results showed that binary mixtures of R-(+)-limonene:xanthoxyline (A:C), vanillin:xanthoxyline (B:C), and xanthoxyline:linoleic acid (C:E) exhibited strong allelopathic activities on germination and seedling growth of the tested plant, and the level of inhibition was close to the effect of xanthoxyline (C) at 400 µM and was better than the effect of xanthoxyline (C) at 200 µM. The inhibition was hypothesized to be from a synergistic interaction of each pair of alleochemicals. Mole ratios of each pair of allelochemicals ((A:C), (B:C), and (C:E)) were then evaluated, and the best ratios of the binary mixtures A:C, B:C and C:E were found to be 2:8, 2:8, and 4:6 respectively. These binary mixtures significantly inhibited germination and shoot and root growth of Chinese amaranth at low concentrations. The results reported here highlight a synergistic behavior of some allelochemicals which could be applied in the development of potential herbicides. Full article

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12 pages, 5021 KiB

Open AccessFeature PaperArticle

Fluorescent “Turn-Off” Detection of Fluoride and Cyanide Ions Using Zwitterionic Spirocyclic Meisenheimer Compounds

by Marina Benet¹

, Marc Villabona¹

, Carles Llavina¹

, Silvia Mena¹

, Jordi Hernando^1,*

, Rabih O. Al-Kaysi^2,*

and Gonzalo Guirado^1,*

¹ Departament de Química, Universitat Autònoma de Barcelona, E-08193 Bellaterra, 08193 Barcelona, Spain

² College of Science and Health Professions-3124, King Saud bin Abdulaziz University for Health Sciences/King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, 11426 Riyadh, Saudi Arabia

Molecules 2017, 22(11), 1842; https://doi.org/10.3390/molecules22111842 - 27 Oct 2017

Cited by 13 | Viewed by 6122

Abstract

Stable zwitterionic spirocyclic Meisenheimer compounds were synthesized using a one-step reaction between picric acid and diisopropyl (ZW1) or dicyclohexyl (ZW3) carbodiimide. A solution of these compounds displays intense orange fluorescence upon UV or visible light excitation, which can be quenched or “turned-off” by [...] Read more.

Stable zwitterionic spirocyclic Meisenheimer compounds were synthesized using a one-step reaction between picric acid and diisopropyl (ZW1) or dicyclohexyl (ZW3) carbodiimide. A solution of these compounds displays intense orange fluorescence upon UV or visible light excitation, which can be quenched or “turned-off” by adding a mole equivalent amount of F⁻ or CN⁻ ions in acetonitrile. Fluorescence is not quenched in the presence of other ions such as Cl⁻, Br⁻, I⁻, NO₂⁻, NO₃⁻, or H₂PO₄⁻. These compounds can therefore be utilized as practical colorimetric and fluorescent probes for monitoring the presence of F⁻ or CN⁻ anions. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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15 pages, 2240 KiB

Open AccessArticle

Thymosin α1 Interacts with Hyaluronic Acid Electrostatically by Its Terminal Sequence LKEKK

by Walter Mandaliti¹, Ridvan Nepravishta^1,2, Francesca Pica³

, Paola Sinibaldi Vallebona³, Enrico Garaci⁴ and Maurizio Paci^1,*

¹ Department of Chemical Sciences and Technologies, University of Rome “Tor Vergata”, via della Ricerca Scientifica 1, 00133 Rome, Italy

² School of Pharmacy, East Anglia University, Norwich NR4 7TJ, UK

³ Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, via Montpellier 1, 00133 Rome, Italy

⁴ San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, Italy

Molecules 2017, 22(11), 1843; https://doi.org/10.3390/molecules22111843 - 27 Oct 2017

Cited by 13 | Viewed by 6988

Abstract

Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into [...] Read more.

Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of Tα1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1 and is suggestive of a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression. Full article

(This article belongs to the Special Issue Hyaluronic Acid and its Derivatives for Biomedical Applications)

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11 pages, 1790 KiB

Open AccessArticle

Surface-Relief Gratings in Halogen-Bonded Polymer–Azobenzene Complexes: A Concentration-Dependence Study

by Jelle E. Stumpel^1,2, Marco Saccone^1,†

, Valentina Dichiarante³

, Ossi Lehtonen², Matti Virkki¹

, Pierangelo Metrangolo^2,3 and Arri Priimagi^1,*

¹ Laboratory of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 541, FI-33101 Tampere, Finland

² Department of Applied Physics, Aalto University, P.O. Box 15100, FI-00076 Espoo, Finland

³ Laboratory of Supramolecular and Bio-Nanomaterials (SupraBioNanoLab), Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, Via L. Mancinelli 7, I-20131 Milano, Italy

^† Present address: Institute of Organic Chemistry, University of Duisburg-Essen, Universitätstraße 7, 45117 Essen, Germany.

Molecules 2017, 22(11), 1844; https://doi.org/10.3390/molecules22111844 - 28 Oct 2017

Cited by 12 | Viewed by 4845

Abstract

In recent years, supramolecular complexes comprising a poly(4-vinylpyridine) backbone and azobenzene-based halogen bond donors have emerged as a promising class of materials for the inscription of light-induced surface-relief gratings (SRGs). The studies up to date have focused on building supramolecular hierarchies, i.e., optimizing [...] Read more.

In recent years, supramolecular complexes comprising a poly(4-vinylpyridine) backbone and azobenzene-based halogen bond donors have emerged as a promising class of materials for the inscription of light-induced surface-relief gratings (SRGs). The studies up to date have focused on building supramolecular hierarchies, i.e., optimizing the polymer–azobenzene noncovalent interaction for efficient surface patterning. They have been conducted using systems with relatively low azobenzene content, and little is known about the concentration dependence of SRG formation in halogen-bonded polymer–azobenzene complexes. Herein, we bridge this gap, and study the concentration dependence of SRG formation using two halogen-bond-donating azobenzene derivatives, one functionalized with a tetrafluoroiodophenyl and the other with an iodoethynylphenyl group. Both have been previously identified as efficient molecules in driving the SRG formation. We cover a broad concentration range, starting from 10 mol % azobenzene content and going all the way up to equimolar degree of complexation. The complexes are studied as spin-coated thin films, and analyzed by optical microscopy, atomic force microscopy, and optical diffraction arising during the SRG formation. We obtained diffraction efficiencies as high as 35%, and modulation depths close to 400 nm, which are significantly higher than the values previously reported for halogen-bonded polymer–azobenzene complexes. Full article

(This article belongs to the Special Issue Photoresponsive Polymers)

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12 pages, 3049 KiB

Open AccessArticle

Margination of Fluorescent Polylactic Acid–Polyaspartamide based Nanoparticles in Microcapillaries In Vitro: the Effect of Hematocrit and Pressure

by Emanuela Fabiola Craparo^1,†, Rosa D’Apolito^2,†, Gaetano Giammona^1,3,4, Gennara Cavallaro^1,* and Giovanna Tomaiuolo^2,5

¹ Laboratory of Biocompatible Polymers, Dipartimento di Scienze e Tecnologie, Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo-via Archirafi, 32-90123 Palermo, Italy

² Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università di Napoli Federico II, P.le V. Tecchio 80, 80125 Napoli, Italy

³ IBF-CNR, 90143 Palermo, Italy

⁴ Mediterranean Center for Human Health Advanced Biotechnologies (CHAB), ATeNCenter, University of Palermo, 90100 Palermo, Italy

⁵ CEINGE Biotecnologie avanzate, Via Gaetano Salvatore 486, 80145 Napoli, Italy

^† The two authors contributed equally to this work.

Molecules 2017, 22(11), 1845; https://doi.org/10.3390/molecules22111845 - 28 Oct 2017

Cited by 4 | Viewed by 4691

Abstract

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration [...] Read more.

The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier–wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop. As model drug carriers, fluorescent polymeric nanoparticles (FNPs) were chosen, which were obtained by using as starting material a pegylated polylactic acid–polyaspartamide copolymer. The latter was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) with Rhodamine (RhB), polylactic acid (PLA) and then poly(ethyleneglycol) (PEG) chains. It was found that the carrier concentration near the wall increases with increasing pressure drop, independently of RBC concentration, and that the tendency for FNP margination decreases with increasing hematocrit. This work highlights the importance of taking into account RBC–drug carrier interactions and physiological conditions in microcirculation when planning a drug delivery strategy based on systemically administered carriers. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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9 pages, 888 KiB

Open AccessArticle

Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF_13-25 Fragment

by Beatriz Balsera¹, M. Ángeles Bonache¹, Marie Reille-Seroussi², Nathalie Gagey-Eilstein², Michel Vidal^2,3, Rosario González-Muñiz¹ and María Jesús Pérez de Vega^1,*

¹ Instituto de Química-Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, Spain

² UMR 8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, 4 avenue de l’Observatoire, Paris 75006, France

³ UF “Pharmacocinétique et Pharmacochimie”, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, Paris 75014, France

Molecules 2017, 22(11), 1846; https://doi.org/10.3390/molecules22111846 - 28 Oct 2017

Cited by 7 | Viewed by 4586

Abstract

The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of [...] Read more.

The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEX⁵ARNX⁹AAX¹²N-NH₂), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1). This study led to the discovery of some new, quite potent inhibitors of this protein–protein system. The results we found prompted us to extend the study to other peptides of the library. We describe here the evaluation of a new selection of peptides from the initial library that allow us to identify new VEGF-VEGFR1 inhibitors. Among them, the peptide sequence containing F, W, and I residues at the 5, 9, and 12 positions, show a very significant nanomolar IC₅₀ value, competing with VEGF for its receptor 1, VEGFR1 (Flt-1), which could represent a new tool within the therapeutic arsenal for cancer detection and therapy. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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13 pages, 1745 KiB

Open AccessArticle

Berberine Activates Aryl Hydrocarbon Receptor but Suppresses CYP1A1 Induction through miR-21-3p Stimulation in MCF-7 Breast Cancer Cells

by Sheng-Nan Lo^1,2, Chun-Wei Wang^1,2, Yueh-Shieh Chen¹, Chiung-Chiao Huang¹, Tian-Shung Wu³, Lih-Ann Li⁴, I-Jung Lee⁵ and Yune-Fang Ueng^1,2,6,7,*

¹ Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei 112, Taiwan

² Institute of Biopharmaceutical Sciences, School of Pharmacy, National Yang-Ming University, Taipei 112, Taiwan

³ Department of Chemistry, National Cheng-Kung University, Tainen 701, Taiwan

⁴ National Institute of Environmental Health Sciences, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan

⁵ Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei 112, Taiwan

⁶ Institute of Medical Sciences, Taipei Medical University, Taipei 101, Taiwan

⁷ Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

Molecules 2017, 22(11), 1847; https://doi.org/10.3390/molecules22111847 - 28 Oct 2017

Cited by 32 | Viewed by 6726

Abstract

Berberine and the methylenedioxy ring-opening derivatives palmatine and jatrorrhizine are active ingredients in immunomodulatory plants, such as goldenseal. This study aimed to illustrate the effects of protoberberines on aryl hydrocarbon receptor (AhR) activation and cytochrome P450 (CYP) 1 in the estrogen receptor (ER)α(+) [...] Read more.

Berberine and the methylenedioxy ring-opening derivatives palmatine and jatrorrhizine are active ingredients in immunomodulatory plants, such as goldenseal. This study aimed to illustrate the effects of protoberberines on aryl hydrocarbon receptor (AhR) activation and cytochrome P450 (CYP) 1 in the estrogen receptor (ER)α(+) MCF-7 breast cancer cells. Among protoberberines at non-cytotoxic concentrations (≤10 μM), berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. The 24-h exposure to 10 μM berberine did not change CYP1A1 mRNA stability, protein level and function. Berberine significantly increased micro RNA (miR)-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 protein with a 50% increase. These findings demonstrate that the ring opening of the methylenedioxyl moiety in berberine decreased AhR activation in MCF-7 cells. While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression. 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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38 pages, 5477 KiB

Open AccessConference Report

The Forty-Sixth Euro Congress on Drug Synthesis and Analysis: Snapshot ^†

by Pavel Mucaji^1,*, Atanas G. Atanasov^2,3,*

, Andrzej Bak⁴

, Violetta Kozik⁵, Karolina Sieron⁶, Mark Olsen⁷, Weidong Pan^8,9, Yazhou Liu^8,9, Shengchao Hu^8,9, Junjie Lan^8,9, Norbert Haider¹⁰, Robert Musiol⁴, Jan Vanco¹¹, Marc Diederich¹²

, Seungwon Ji¹², Jan Zitko¹³, Dongdong Wang^2,3, Danica Agbaba¹⁴, Katarina Nikolic¹⁴, Slavica Oljacic¹⁴, Jelica Vucicevic¹⁴, Daniela Jezova¹⁵

, Anna Tsantili-Kakoulidou¹⁶

, Fotios Tsopelas¹⁷

, Constantinos Giaginis¹⁸, Teresa Kowalska⁴

, Mieczyslaw Sajewicz⁴

, Jerzy Silberring¹⁹, Przemyslaw Mielczarek¹⁹

, Marek Smoluch¹⁹, Izabela Jendrzejewska²⁰, Jaroslaw Polanski⁴ and Josef Jampilek^21,*

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¹ Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia

² Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Postepu 36A, 05-552 Jastrzebiec, Poland

³ Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria

⁴ Institute of Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland

⁵ Department of Synthesis Chemistry, Faculty of Mathematics, Physics and Chemistry, University of Silesia, Szkolna 9, 40007 Katowice, Poland

⁶ Department of Physical Medicine, Medical University of Silesia, Medykow 18, 40752 Katowice, Poland

⁷ Department of Pharmaceutical Sciences, College of Pharmacy Glendale, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA

⁸ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, China

⁹ Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 3491 Baijin Road, Guiyang, 550014, China

¹⁰ Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria

¹¹ Department of Inorganic Chemistry & Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, 17. listopadu 12, 77146 Olomouc, Czech Republic

¹² Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Seoul 08826, Korea

¹³ Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 50005 Hradec Kralove, Czech Republic

¹⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia

¹⁵ Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovakia

¹⁶ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece

¹⁷ Laboratory of Inorganic and Analytical Chemistry, School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou 9, 15780 Athens, Greece

¹⁸ Department of Food Science and Nutrition, School of Environment, University of the Aegean, 81400 Myrina, Lemnos, Greece

¹⁹ Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Mickiewicza 30, 30059 Krakow, Poland

²⁰ Department of Crystallography, Faculty of Mathematics, Physics and Chemistry, University of Silesia, Bankowa 12, 40006 Katowice, Poland

²¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia

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Molecules 2017, 22(11), 1848; https://doi.org/10.3390/molecules22111848 - 28 Oct 2017

Cited by 5 | Viewed by 7109

Abstract

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical [...] Read more.

The 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017) was arranged within the celebration of the 65th Anniversary of the Faculty of Pharmacy at Comenius University in Bratislava, Slovakia from 5–8 September 2017 to get together specialists in medicinal chemistry, organic synthesis, pharmaceutical analysis, screening of bioactive compounds, pharmacology and drug formulations; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topic of the conference, “Drug Synthesis and Analysis,” meant that the symposium welcomed all pharmacists and/or researchers (chemists, analysts, biologists) and students interested in scientific work dealing with investigations of biologically active compounds as potential drugs. The authors of this manuscript were plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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14 pages, 4404 KiB

Open AccessArticle

Polyphosphates as Inhibitors for Poly(vinyl Chloride) Photodegradation

by Dina S. Ahmed¹, Gamal A. El-Hiti^2,*

, Emad Yousif^3,* and Ayad S. Hameed¹

¹ Department of Chemistry, College of Science, Tikrit University, Tikrit 34001, Iraq

² Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia

³ Department of Chemistry, College of Science, Al-Nahrain University, Baghdad 64021, Iraq

Molecules 2017, 22(11), 1849; https://doi.org/10.3390/molecules22111849 - 28 Oct 2017

Cited by 49 | Viewed by 5055

Abstract

Three polyphosphates were used as inhibitors for poly(vinyl chloride) (PVC) photodegradation. The polyphosphates were added to PVC at a concentration of 0.5% by weight. The PVC films (40 µm thickness) were irradiated at room temperature with ultraviolet (UV) light for up to 300 [...] Read more.

Three polyphosphates were used as inhibitors for poly(vinyl chloride) (PVC) photodegradation. The polyphosphates were added to PVC at a concentration of 0.5% by weight. The PVC films (40 µm thickness) were irradiated at room temperature with ultraviolet (UV) light for up to 300 h. The changes in PVC films after irradiation were monitored by Fourier transform infrared spectroscopy, weight loss, viscosity-average molecular weight determination, and atomic force microscopy. These changes were very noticeable in the blank PVC films compared to the ones obtained when additives were used. The polyphosphates can inhibit the PVC photodegradation through direct absorption of UV light, interactions with PVC chains, and acting as radical scavengers. Full article

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20 pages, 11454 KiB

Open AccessArticle

Sustainable Bio-Based Phenol-Formaldehyde Resoles Using Hydrolytically Depolymerized Kraft Lignin

by Homaira Siddiqui¹, Nubla Mahmood¹, Zhongshun Yuan¹, Ferdinando Crapulli¹, Luana Dessbesell², Amin Rizkalla¹, Ajay Ray^1,* and Chunbao (Charles) Xu^1,*

¹ Department of Chemical and Biochemical Engineering, Faculty of Engineering, Western University, London, Ontario N6A 5B9, Canada

² Faculty of Natural Resources Management, Lakehead University, Thunder Bay, Ontario P7B 5E1, Canada

Molecules 2017, 22(11), 1850; https://doi.org/10.3390/molecules22111850 - 28 Oct 2017

Cited by 37 | Viewed by 7874

Abstract

In this study bio-based bio-phenol-formaldehyde (BPF) resoles were prepared using hydrolytically depolymerized Kraft lignin (DKL) as bio-phenol to partially substitute phenol. The effects of phenol substitution ratio, weight-average molecular weight (M_w) of DKL and formaldehyde-to-phenol (F/P) ratio were also investigated [...] Read more.

In this study bio-based bio-phenol-formaldehyde (BPF) resoles were prepared using hydrolytically depolymerized Kraft lignin (DKL) as bio-phenol to partially substitute phenol. The effects of phenol substitution ratio, weight-average molecular weight (M_w) of DKL and formaldehyde-to-phenol (F/P) ratio were also investigated to find the optimum curing temperature for BPF resoles. The results indicated that DKL with M_w ~ 1200 g/mol provides a curing temperature of less than 180 °C for any substitution level, provided that F/P ratios are controlled. Incorporation of lignin reduced the curing temperature of the resin, however, higher M_w DKL negatively affected the curing process. For any level of lignin M_w, the curing temperature was found to increase with lower F/P ratios at lower phenol substitution levels. At 25% and 50% phenol substitution, increasing the F/P ratio allows for synthesis of resoles with lower curing temperatures. Increasing the phenol substitution from 50% to 75% allows for a broader range of lignin M_w to attain low curing temperatures. Full article

(This article belongs to the Special Issue Lignin for Energy, Chemicals and Materials)

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18 pages, 3601 KiB

Open AccessArticle

Marrubium vulgare L. Leave Extract: Phytochemical Composition, Antioxidant and Wound Healing Properties

by Bédis Amri¹, Emanuela Martino^2,3,*

, Francesca Vitulo⁴

, Federica Corana⁵, Leila Bettaieb-Ben Kaâb¹, Marta Rui⁶, Daniela Rossi⁶, Michela Mori⁶, Silvia Rossi^3,6

and Simona Collina^3,6,*

¹ Département de Biologie, Faculté des Sciences de Tunis el Manar, Unité de recherche ‘Nutrition et métabolismes azoté et protéines de stress’ (99 UR/09-20), 1002 Tunis, Tunisia

² Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy

³ Centre for Health Technologies (CHT), University of Pavia, Viale Taramelli 12, Pavia 27100, Italy

⁴ Indena S.p.A., Via Don Minzoni, 6, 20090 Settala, Italy

⁵ Centro Grandi Strumenti (CGS), University of Pavia, Via Bassi 21, 27100 Pavia, Italy

⁶ Department of Drug Sciences, Medicinal Chemistry section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy

Molecules 2017, 22(11), 1851; https://doi.org/10.3390/molecules22111851 - 28 Oct 2017

Cited by 67 | Viewed by 9645

Abstract

Several factors contribute in wound generation, e.g., accidental traumas or surgery, and in certain cases, this dermal injury may have a devastating outcome. When skin damage occurs, the human body puts in place a sophisticated choreography, which involves numerous repairing processes to restore [...] Read more.

Several factors contribute in wound generation, e.g., accidental traumas or surgery, and in certain cases, this dermal injury may have a devastating outcome. When skin damage occurs, the human body puts in place a sophisticated choreography, which involves numerous repairing processes to restore physiological conditions. Nevertheless, natural healing mechanisms are ineffective towards chronic or non-healing wounds and thus, therapeutic strategies may represent the only beneficial alternative to counteract these tissue insults. Over the years, numerous studies showed the great potential of plants in promoting wound healing, by virtue of their high contents in antioxidant species. These compounds trigger a molecular cascade that collimate into the promotion of reparative processes. In this article, we report on the potential effect on wound healing of Marrubium vulgare L., a medicinal plant well known for several pharmaceutical activities. To this aim, the methanolic extract was prepared and subjected to a phytochemical investigation, quantifying the amount of marrubiin via NMR and drawing the phytochemical fingerprint via high performance liquid chromatography—ultra violet/photodiode-array detection-electrospray/mass (HPLC-UV/PAD-ESI/MS) analysis. Lastly, the antioxidant properties and wound healing potential have been evaluated. Full article

(This article belongs to the Collection Herbal Medicine Research)

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22 pages, 9849 KiB

Open AccessArticle

Biological Properties of Low-Toxic PLGA and PLGA/PHB Fibrous Nanocomposite Scaffolds for Osseous Tissue Regeneration. Evaluation of Potential Bioactivity

by Boguslawa Żywicka¹

, Izabella Krucińska², Jerzy Garcarek³, Maria Szymonowicz¹, Agnieszka Komisarczyk^2,* and Zbigniew Rybak¹

¹ Department of Experimental Surgery and Biomaterials Research, Wrocław Medical University, Pasteura 1, 50-367 Wrocław, Poland

² Department of Material and Commodity Sciences and Textile Metrology, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland

³ Department of General Radiology, Interventional Radiology and Neuroradiology, Wrocław Medical University, Pasteura 1, 50-367 Wrocław, Poland

Molecules 2017, 22(11), 1852; https://doi.org/10.3390/molecules22111852 - 28 Oct 2017

Cited by 12 | Viewed by 5018

Abstract

Abstracts: The aim of the study was to evaluate the biocompatibility and bioactivity of two new prototype implants for bone tissue regeneration made from biodegradable fibrous materials. The first is a newly developed poly(l-lactide-co-glycolide), (PLGA), and the second is a blend of [...] Read more.

Abstracts: The aim of the study was to evaluate the biocompatibility and bioactivity of two new prototype implants for bone tissue regeneration made from biodegradable fibrous materials. The first is a newly developed poly(l-lactide-co-glycolide), (PLGA), and the second is a blend of PLGA with synthetic poly([R,S]-3-hydroxybutyrate) (PLGA/PHB). The implant prototypes comprise PLGA or PLGA/PHB nonwoven fabrics with designed pore structures to create the best conditions for cell proliferation. The bioactivity of the proposed implants was enhanced by introducing a hydroxyapatite material and a biologically active agent, namely, growth factor IGF1, encapsulated in calcium alginate microspheres. To assess the biocompatibility and bioactivity, allergenic tests and an assessment of the local reaction of bone tissue after implantation were performed. Comparative studies of local tissue response after implantation into trochanters for a period of 12 months were performed on New Zealand rabbits. Based on the results of the in vivo evaluation of the allergenic effects and the local tissue reaction 12 months after implantation, it was concluded that the two implant prototypes, PLGA + IGF1 and PLGA/PHB + IGF1, were characterized by high biocompatibility with the soft and bone tissues of the tested animals. Full article

(This article belongs to the Special Issue Biomedical Applications of Polylactide (PLA) and its Copolymers)

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21 pages, 1367 KiB

Open AccessArticle

Simultaneous Determination of Twenty-Five Compounds in Rat Plasma Using Ultra-High Performance Liquid Chromatography-Polarity Switching Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study

by Na Zhang^1,2,†, Yueting Li^1,†, Jing Sun¹, Chun Li¹, Yuelin Song¹, Jun Li¹

, Pengfei Tu¹ and Yunfang Zhao^1,*

¹ Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China

² Department of pharmacy, Baotou Medical College, Baotou 014060, China

^† These authors contributed equally to this article.

Molecules 2017, 22(11), 1853; https://doi.org/10.3390/molecules22111853 - 30 Oct 2017

Cited by 6 | Viewed by 4208

Abstract

An attempt was made to characterize the pharmacokinetic profiles of Qishen Keli (QSKL) that has been widely proved to be effective in clinical practice. A method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 25 [...] Read more.

An attempt was made to characterize the pharmacokinetic profiles of Qishen Keli (QSKL) that has been widely proved to be effective in clinical practice. A method using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of 25 analytes in rat plasma was developed and validated. Satisfactory chromatographic separation was achieved on an ACQUITY UPLC HSS T3 column with gradient elution using mobile phase consisting of 0.02% aqueous formic acid (A) and acetonitrile fortified with 0.02% formic acid (B), and analyte detection was carried out using polarity-switching multiple reaction monitoring mode. Method validation assays in terms of selectivity, linearity, inter- and intra-day variations, matrix effect, and recovery demonstrated the newly developed method to be specific, sensitive, accurate, and precise. Following the oral administration of QSKL at a single dose, the qualified method was successfully applied for pharmacokinetic investigations in sham and model rats. Mild differences occurred for the pharmacokinetic patterns of most components between those two groups, whereas significant differences were observed for glycyrrhizic acid and glycyrrhetic acid. The obtained findings could provide meaningful information for the clarification of the effective material basis of QSKL. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 1497 KiB

Open AccessArticle

Functional Characterization of a Hydroxyacid/Alcohol Hydroxycinnamoyl Transferase Produced by the Liverwort Marchantia emarginata

by Ping-Ping Wang, Hui Liu, Shuai Gao and Ai-Xia Cheng^*

Key Laboratory of Chemical Biology of Natural Products, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China

Molecules 2017, 22(11), 1854; https://doi.org/10.3390/molecules22111854 - 31 Oct 2017

Cited by 3 | Viewed by 4451

Abstract

The aerial organs of most terrestrial plants are covered by a hydrophobic protective cuticle. The main constituent of the cuticle is the lipid polyester cutin, which is composed of aliphatic and aromatic domains. The aliphatic component is a polyester between fatty acid/alcohol and [...] Read more.

The aerial organs of most terrestrial plants are covered by a hydrophobic protective cuticle. The main constituent of the cuticle is the lipid polyester cutin, which is composed of aliphatic and aromatic domains. The aliphatic component is a polyester between fatty acid/alcohol and hydroxycinnamoyl acid. The BAHD/HxxxD family enzymes are central to the synthesis of these polyesters. The nature of this class of enzymes in bryophytes has not been explored to date. Here, a gene encoding a fatty ω-hydroxyacid/fatty alcohol hydroxycinnamoyl transferase (HFT) has been isolated from the liverwort Marchantia emarginata and has been functionally characterized. Experiments based on recombinant protein showed that the enzyme uses ω-hydroxy fatty acids or primary alcohols as its acyl acceptor and various hydroxycinnamoyl-CoAs—preferentially feruloyl-CoA and caffeoyl-CoA—as acyl donors at least in vitro. The transient expression of a MeHFT-GFP fusion transgene in the Nicotiana benthamiana leaf demonstrated that MeHFT is directed to the cytoplasm, suggesting that the feruloylation of cutin monomers takes place there. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 6182 KiB

Open AccessArticle

¹H-NMR-Based Metabonomics of the Protective Effect of Coptis chinensis and Berberine on Cinnabar-Induced Hepatotoxicity and Nephrotoxicity in Rats

by Guangyue Su³, Haifeng Wang^1,2

, Yuxian Gao¹, Gang Chen^1,2, Yuehu Pei^1,2 and Jiao Bai^1,2,*

¹ Department of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

² Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

³ School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2017, 22(11), 1855; https://doi.org/10.3390/molecules22111855 - 2 Nov 2017

Cited by 21 | Viewed by 6802

Abstract

Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which [...] Read more.

Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics. Full article

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

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10 pages, 2008 KiB

Open AccessFeature PaperArticle

Zinc Ion-Dependent Peptide Nucleic Acid-Based Artificial Enzyme that Cleaves RNA—Bulge Size and Sequence Dependence

by Merita Murtola^1,2,*, Alice Ghidini², Pasi Virta¹ and Roger Strömberg^2,*

¹ Department of Chemistry, University of Turku, 20014 Turku, Finland

² Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83 Huddinge, Stockholm, Sweden

Molecules 2017, 22(11), 1856; https://doi.org/10.3390/molecules22111856 - 29 Oct 2017

Cited by 16 | Viewed by 5677

Abstract

In this report, we investigate the efficiency and selectivity of a Zn²⁺-dependent peptide nucleic acid-based artificial ribonuclease (PNAzyme) that cleaves RNA target sequences. The target RNAs are varied to form different sizes (3 and 4 nucleotides, nt) and sequences in the [...] Read more.

In this report, we investigate the efficiency and selectivity of a Zn²⁺-dependent peptide nucleic acid-based artificial ribonuclease (PNAzyme) that cleaves RNA target sequences. The target RNAs are varied to form different sizes (3 and 4 nucleotides, nt) and sequences in the bulge formed upon binding to the PNAzyme. PNAzyme-promoted cleavage of the target RNAs was observed and variation of the substrate showed a clear dependence on the sequence and size of the bulge. For targets that form 4-nt bulges, we identified systems with an improved efficacy (an estimated half-life of ca 7–8 h as compared to 11–12 h for sequences studied earlier) as well as systems with an improved site selectivity (up to over 70% cleavage at a single site as compared to 50–60% with previous targets sequences). For targets forming 3-nt bulges, the enhancement compared to previous systems was even more pronounced. Compared to a starting point of targets forming 3-nt AAA bulges (half-lives of ca 21–24 h), we could identify target sequences that were cleaved with half-lives three times lower (ca 7–8 h), i.e., at rates similar to those found for the fastest 4-nt bulge system. In addition, with the 3-nt bulge RNA target site selectivity was improved even further to reach well over 80% cleavage at a specific site. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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13 pages, 2305 KiB

Open AccessArticle

Synthesis and Antitumor Activity of Novel Arylpiperazine Derivatives Containing the Saccharin Moiety

by Hong Chen^1,†, Bing-Bing Xu^2,†, Tao Sun¹, Zhan Zhou¹, Hui-Yuan Ya^1,* and Mu Yuan^2,*

¹ College of Food and Drug, Luoyang Normal University, 6# Jiqing Road, Luoyang 471934, China

² Pharmaceutical Research Center, Guangzhou Medical University, 195# Dongfengxi Road, Guangzhou 511436, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1857; https://doi.org/10.3390/molecules22111857 - 29 Oct 2017

Cited by 14 | Viewed by 4999

Abstract

Prostate cancer is a major public health problem worldwide. For the development of potential anti-prostate cancer agents, a series of novel arylpiperazine derivatives containing the saccharin moiety based on previous studies was designed, synthesized, and evaluated in prostate (PC-3, LNCaP, and DU145) cancer [...] Read more.

Prostate cancer is a major public health problem worldwide. For the development of potential anti-prostate cancer agents, a series of novel arylpiperazine derivatives containing the saccharin moiety based on previous studies was designed, synthesized, and evaluated in prostate (PC-3, LNCaP, and DU145) cancer cell lines for their anticancer activities. The majority of the compounds exhibited excellent selective activity for the tested cancer cells. Compounds 4 and 12 exhibited strong cytotoxic activities against DU145 cells (half maximal inhibitory concentration (IC₅₀) < 2 μM). The structure–activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data. This work provides a potential lead compound for anticancer agent development focusing on prostate cancer therapy. 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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20 pages, 3080 KiB

Open AccessArticle

Olive (Olea europaea L.) Biophenols: A Nutriceutical against Oxidative Stress in SH-SY5Y Cells

by Syed Haris Omar^1,2,*

, Philip G. Kerr^1,2

, Christopher J. Scott^1,2, Adam S. Hamlin³ and Hassan K. Obied^1,2

¹ School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia

² Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW 2678, Australia

³ School of Science & Technology, University of New England, Armidale, NSW 2351, Australia

Molecules 2017, 22(11), 1858; https://doi.org/10.3390/molecules22111858 - 29 Oct 2017

Cited by 41 | Viewed by 10322

Abstract

Plant biophenols have been shown to be effective in the modulation of Alzheimer’s disease (AD) pathology resulting from free radical-induced oxidative stress and imbalance of the redox chemistry of transition metal ions (e.g., iron and copper). On the basis of earlier reported pharmacological [...] Read more.

Plant biophenols have been shown to be effective in the modulation of Alzheimer’s disease (AD) pathology resulting from free radical-induced oxidative stress and imbalance of the redox chemistry of transition metal ions (e.g., iron and copper). On the basis of earlier reported pharmacological activities, olive biophenols would also be expected to have anti-Alzheimer’s activity. In the present study, the antioxidant activity of individual olive biophenols (viz. caffeic acid, hydroxytyrosol, oleuropein, verbascoside, quercetin, rutin and luteolin) were evaluated using superoxide radical scavenging activity (SOR), hydrogen peroxide (H₂O₂) scavenging activity, and ferric reducing ability of plasma (FRAP) assays. The identification and antioxidant activities in four commercial olive extracts—Olive leaf extract^TM (OLE), Olive fruit extract^TM (OFE), Hydroxytyrosol Extreme^TM (HTE), and Olivenol plus^TM (OLP)—were evaluated using an on-line HPLC-ABTS^•+ assay, and HPLC-DAD-MS analysis. Oleuropein and hydroxytyrosol were the predominant biophenols in all the extracts. Among the single compounds examined, quercetin (EC₅₀: 93.97 μM) and verbascoside (EC₅₀: 0.66 mM) were the most potent SOR and H₂O₂ scavengers respectively. However, OLE and HTE were the highest SOR (EC₅₀: 1.89 μg/mL) and H₂O₂ (EC₅₀: 115.8 μg/mL) scavengers among the biophenol extracts. The neuroprotection of the biophenols was evaluated against H₂O₂-induced oxidative stress and copper (Cu)-induced toxicity in neuroblastoma (SH-SY5Y) cells. The highest neuroprotection values (98% and 92%) against H₂O₂-induced and Cu-induced toxicities were shown by the commercial extract HTE^TM. These were followed by the individual biophenols, caffeic acid (77% and 64%) and verbascoside (71% and 72%). Our results suggest that olive biophenols potentially serve as agents for the prevention of neurodegenerative diseases such as AD, and other neurodegenerative ailments that are caused by oxidative stress. Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

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8 pages, 1032 KiB

Open AccessArticle

New Adducts of Iriflophene and Flavonoids Isolated from Sedum aizoon L. with Potential Antitumor Activity

by Mingxiao Li, Zheyuan Qi, Yimeng Hao, Chongning Lv, Lingyun Jia, Jing Wang and Jincai Lu^*

Department of Medicinal Plants, school of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2017, 22(11), 1859; https://doi.org/10.3390/molecules22111859 - 2 Nov 2017

Cited by 18 | Viewed by 4757

Abstract

Four new special compounds with character of an iriflophene unit and a flavonoid unit connecting via a furan ring were isolated from the roots of Sedum aizoon L. Their corresponding structures were elucidated on the basis of spectroscopic analysis. The in vitro anti-proliferative [...] Read more.

Four new special compounds with character of an iriflophene unit and a flavonoid unit connecting via a furan ring were isolated from the roots of Sedum aizoon L. Their corresponding structures were elucidated on the basis of spectroscopic analysis. The in vitro anti-proliferative activities against BXPC-3, A549, and MCF-7 tumor cell lines were evaluated. Compounds 3 and 4 exhibited moderate cytotoxic activities with IC₅₀ ranging from 24.84 to 37.22 μmol L⁻¹, which was capable for further drug exploration. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1507 KiB

Open AccessArticle

Coordination Polymers Containing 1,3-Phenylenebis-((1H-1,2,4-triazol-1-yl)methanone) Ligand: Synthesis and ε-Caprolactone Polymerization Behavior

by Nestor J. Bello-Vieda¹

, Ricardo A. Murcia¹, Alvaro Muñoz-Castro^2,3, Mario A. Macías¹ and John J. Hurtado^1,*

¹ Department of Chemistry, Universidad de los Andes, Carrera 1 N° 18A-12, Bogotá 111711, Colombia

² Grupo de Química Inorgánica y Materiales Moleculares, Universidad Autonoma de Chile, El Llano Subercaseaux 2801, Santiago 8910060, Chile

³ Relativistic Molecular Physics (ReMoPh) Group, Universidad Andres Bello, Republica 275, Santiago, Chile

Molecules 2017, 22(11), 1860; https://doi.org/10.3390/molecules22111860 - 10 Nov 2017

Cited by 6 | Viewed by 4741

Abstract

The reaction of isophthaloyl dichloride with 1H-1,2,4-triazole afforded the new ligand 1,3-phenylenebis(1,2,4-triazole-1-yl)methanone (1). A series of Co(II), Cu(II), Zn(II) and Ni(II) complexes were synthesized using 1 and then characterized by melting point analysis, elemental analysis, theoretical calculations, thermogravimetric analysis, [...] Read more.

The reaction of isophthaloyl dichloride with 1H-1,2,4-triazole afforded the new ligand 1,3-phenylenebis(1,2,4-triazole-1-yl)methanone (1). A series of Co(II), Cu(II), Zn(II) and Ni(II) complexes were synthesized using 1 and then characterized by melting point analysis, elemental analysis, theoretical calculations, thermogravimetric analysis, X-ray powder diffraction, nuclear magnetic resonance, infrared and Raman spectroscopy. Experimental and computational studies predict the formation of coordination polymers (CPs). The cobalt and copper CPs and zinc(II) complex were found to be good initiators for the ring-opening polymerization of ε-caprolactone (CL) under solvent-free conditions. ¹H-NMR analysis showed that the obtained polymers of CL were mainly linear and had terminal hydroxymethylene groups. Differential scanning calorimetry showed that the obtained polycaprolactones had high crystallinity, and TGA showed that they had decomposition temperatures above 400 °C. These results provide insight and guidance for the design of metal complexes with potential applications in the polymerization of CL. Full article

(This article belongs to the Section Organometallic Chemistry)

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12 pages, 1050 KiB

Open AccessArticle

Metabolomic Analysis of Two Parmotrema Lichens: P. robustum (Degel.) Hale and P. andinum (Mull. Arg.) Hale Using UHPLC-ESI-OT-MS-MS

by Alfredo Torres-Benítez¹, María Rivera-Montalvo¹, Beatriz Sepúlveda², Olivio N. Castro³, Edgar Nagles¹, Mario J. Simirgiotis^4,5

, Olimpo García-Beltrán^1,*

and Carlos Areche^6,*

¹ Facultad de Ciencias Naturales y Matematicas, Universidad de Ibague, Carrera 22 calle 67, Ibagué 730001, Colombia

² Departamento de Ciencias Químicas, Universidad Andrés Bello, Campus Viña del Mar, Quillota 980, Viña del Mar 2520000, Chile

³ Departamento de Química, Pontificia Universidad Católica del Perú, Lima 15088, Perú

⁴ Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja 5090000, Valdivia

⁵ Center for Interdisciplinary Studies on the Nervous System, Universidad Austral de Chile, Campus Isla Teja 5090000, Valdivia

⁶ Departamento de Química, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 7800024, Chile

Molecules 2017, 22(11), 1861; https://doi.org/10.3390/molecules22111861 - 30 Oct 2017

Cited by 33 | Viewed by 6356

Abstract

Lichens are symbiotic associations of fungi with microalgae and/or cyanobacteria. Lichens belonging to the Parmeliaceae family comprise 2700 species of lichens, including the Parmotrema genus which is composed of 300 species. The metabolites of this genus include depsides, depsidones, phenolics, polysaccharides, lipids, diphenylethers [...] Read more.

Lichens are symbiotic associations of fungi with microalgae and/or cyanobacteria. Lichens belonging to the Parmeliaceae family comprise 2700 species of lichens, including the Parmotrema genus which is composed of 300 species. The metabolites of this genus include depsides, depsidones, phenolics, polysaccharides, lipids, diphenylethers and dibenzofurans, which are responsible for the biological activities reported including antidiabetic, antihelmintic, anticancer, antioxidant, antibacterial, anti-inflammatory, antimitotic, antitumoral, antifungal, and antioxidant enzyme inhibitory. Due to scarce knowledge of metabolomic profiles of Parmotrema species (P. andinum and P. robustum), a full metabolome study based on ultra-high performance liquid chromatography- diode array detector-electrospray ionization-quadrupole-orbitrap-mass-spectrometry (UHPLC-DAD-ESI-Q-orbitrap MS) was performed for a comprehensive characterization of their substances. From the methanolic extracts of these species, a total of 54 metabolites were identified for the first time using this hyphenated technique, including thirty compounds in P. andinum, and thirty-seven in P. robustum. Moreover, two compounds were not identified as known compounds, and could be new structures, according to our data. This report shows that this technique is effective and accurate for rapid chemical identification of lichen substances and the compounds identified could serve as chemotaxonomic markers to differentiate these ruffle lichens. Full article

(This article belongs to the Section Metabolites)

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13 pages, 1507 KiB

Open AccessArticle

New Biflavonoids with α-Glucosidase and Pancreatic Lipase Inhibitory Activities from Boesenbergia rotunda

by Nutputsorn Chatsumpun^†, Boonchoo Sritularak and Kittisak Likhitwitayawuid^*

¹ Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand

^† Present address: Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.

Molecules 2017, 22(11), 1862; https://doi.org/10.3390/molecules22111862 - 30 Oct 2017

Cited by 45 | Viewed by 7361

Abstract

Roots of Boesenbergia rotunda (L.) Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and [...] Read more.

Roots of Boesenbergia rotunda (L.) Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and was subjected to chromatographic separation to identify the active components. Three new biflavonoids of the flavanone-chalcone type (9, 12, and 13) were isolated, along with 12 known compounds. Among the 15 isolates, the three new compounds showed stronger inhibitory activity against α-glucosidase than the drug acarbose but displayed lower pancreatic lipase inhibitory effect than the drug orlistat. The results indicated the potential of B. rotunda roots as a functional food for controlling after-meal blood glucose levels. Full article

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17 pages, 4365 KiB

Open AccessArticle

Benzoic Acid Derivatives with Trypanocidal Activity: Enzymatic Analysis and Molecular Docking Studies toward Trans-Sialidase

by Muhammad Kashif¹

, Antonio Moreno-Herrera¹, Juan Carlos Villalobos-Rocha², Benjamín Nogueda-Torres³, Jaime Pérez-Villanueva⁴, Karen Rodríguez-Villar⁴

, José Lius Medina-Franco⁵

, Peterson De Andrade⁶, Ivone Carvalho⁶ and Gildardo Rivera^1,*

¹ Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elías Piña, Reynosa 88710, Mexico

² Laboratorio de Bioquímica Microbiana, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico

³ Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico

⁴ Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, UAM-X, Ciudad de México 04960, Mexico

⁵ Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México City 04510, Mexico

⁶ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Café s/n, Ribeirão Preto SP 14040-930, Brazil

Molecules 2017, 22(11), 1863; https://doi.org/10.3390/molecules22111863 - 30 Oct 2017

Cited by 20 | Viewed by 8506

Abstract

Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic [...] Read more.

Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC₅₀) was <0.15 µM on the NINOA strain, and LC₅₀ < 0.22 µM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A). Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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15 pages, 1301 KiB

Open AccessArticle

Synthesis and Biological Evaluation of 2H-Indazole Derivatives: Towards Antimicrobial and Anti-Inflammatory Dual Agents

by Jaime Pérez-Villanueva^1,*, Lilián Yépez-Mulia², Ignacio González-Sánchez³

, Juan Francisco Palacios-Espinosa¹, Olivia Soria-Arteche¹, Teresita Del Rosario Sainz-Espuñes¹, Marco A. Cerbón⁴, Karen Rodríguez-Villar¹

, Ana Karina Rodríguez-Vicente¹, Miguel Cortés-Gines¹, Zeltzin Custodio-Galván¹ and Dante B. Estrada-Castro¹

¹ Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México 04960, Mexico

² Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias-Pediatría, IMSS, Ciudad de México 06720, Mexico

³ Catedrático CONACYT comisionado a Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco (UAM-X), Ciudad de México 04960, Mexico

⁴ Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico

Molecules 2017, 22(11), 1864; https://doi.org/10.3390/molecules22111864 - 31 Oct 2017

Cited by 46 | Viewed by 8352

Abstract

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole [...] Read more.

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2,3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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10 pages, 2521 KiB

Open AccessArticle

Synthesis, Biological Evaluation and Molecular Docking Study of 2-Substituted-4,6-Diarylpyrimidines as α-Glucosidase Inhibitors

by Zipeng Gong^1,2,3, Zhenzhen Xie⁴, Jie Qiu⁴ and Guangcheng Wang^4,*

¹ Provincial Key Laboratory of Pharmaceutics in Guizhou Province, Guizhou Medical University, Beijing Road, Guiyang 550004, China

² School of Pharmacy, Guizhou Medical University, 4 Beijing Road, Guiyang 550004, China

³ National Engineering Research Center of Miao’s Medicines, 4 Beijing Road, Guiyang 550004, China

⁴ College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, China

Molecules 2017, 22(11), 1865; https://doi.org/10.3390/molecules22111865 - 30 Oct 2017

Cited by 19 | Viewed by 4530

Abstract

A novel series of 2-substituted-4,6-diarylpyrimidines 6a–6t has been synthesized, characterized by ¹H-NMR, ¹³C-NMR and HRMS, and screened for in vitro α-glucosidase inhibitory activity. The majority of the screened compounds possessed significant α-glucosidase inhibitory activity with IC₅₀ values [...] Read more.

A novel series of 2-substituted-4,6-diarylpyrimidines 6a–6t has been synthesized, characterized by ¹H-NMR, ¹³C-NMR and HRMS, and screened for in vitro α-glucosidase inhibitory activity. The majority of the screened compounds possessed significant α-glucosidase inhibitory activity with IC₅₀ values ranging from 19.6 ± 0.21 to 38.9 ± 0.35 μM, which is more potent than the positive control α-glucosidase inhibitor acarbose (IC₅₀ = 817.38 ± 6.27 μM). Among them, 6j was found to be the most active compound against α-glucosidase with an IC₅₀ of 19.6 ± 0.21 μM. In addition, molecular docking studies were carried out to explore the binding interactions of 2-substituted-4,6-diarylpyrimidine derivatives with α-glucosidase. Full article

(This article belongs to the Section Medicinal Chemistry)

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15 pages, 1592 KiB

Open AccessArticle

Purification, Characterization, and Antioxidant Activity of Polysaccharides Isolated from Cortex Periplocae

by Xiaoli Wang, Yifei Zhang, Zhikai Liu, Mingqin Zhao^* and Pengfei Liu^*

College of Tobacco Science/National Tobacco Cultivation & Physiology & Biochemistry Research Center, Henan Agricultural University, Zhengzhou 450002, China

Molecules 2017, 22(11), 1866; https://doi.org/10.3390/molecules22111866 - 31 Oct 2017

Cited by 40 | Viewed by 5872

Abstract

In this study, crude Cortex Periplocae polysaccharides (CCPPs) were extracted with water. CCPPs were decolored with AB-8 resin and deproteinated using papain-Sevage methods. Then, they were further purified and separated through DEAE-52 anion exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Three [...] Read more.

In this study, crude Cortex Periplocae polysaccharides (CCPPs) were extracted with water. CCPPs were decolored with AB-8 resin and deproteinated using papain-Sevage methods. Then, they were further purified and separated through DEAE-52 anion exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Three main fractions—CPP1, CPP2, and CPP3, (CPPs)—were obtained. The average molecular weights, monosaccharide analysis, surface morphology, and chemical compositions of the CPPs were investigated by high-performance gel permeation chromatography (HPGPC), gas chromatography-mass spectrometry (GC/MS), UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectrum, and nuclear magnetic resonance (NMR). In addition, the antioxidant activities of these three polysaccharides were investigated. The results indicated that all of the CPPs were composed of rhamnose, arabinose, mannose, glucose, and galactose. These three polysaccharides exhibited antioxidant activities in four assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2′-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical, reducing power, and total antioxidant activity in vitro. The data indicated that these three polysaccharides could be utilized as potential natural sources of alternative additives in the functional food, cosmetics, and pharmaceutical industries. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

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18 pages, 2661 KiB

Open AccessArticle

Study of Absorption Characteristics of the Total Saponins from Radix Ilicis Pubescentis in an In Situ Single-Pass Intestinal Perfusion (SPIP) Rat Model by Using Ultra Performance Liquid Chromatography (UPLC)

by Guojun Kuang^1,2,†, Huan Yi^1,†, Mingjuan Zhu¹, Jie Zhou¹, Xueying Shang¹, Zhongxiang Zhao¹, Chenchen Zhu¹, Qiongfeng Liao¹, Shixia Guan¹ and Lei Zhang^1,*

¹ School of Chinese Materia Medica, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510006, China

² Division of Biochemical Drugs, Guangzhou Institute for Drug Control, Guangzhou 510160, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1867; https://doi.org/10.3390/molecules22111867 - 1 Nov 2017

Cited by 10 | Viewed by 4457

Abstract

In contrast to the extensively reported therapeutic activities, far less attention has been paid to the intestinal absorption of the total saponins from Radix Ilicis Pubescentis (in Chinese Mao-Dong-Qing, MDQ). This study aimed to investigate the intestinal absorption characteristics of ilexgenin A (C1), [...] Read more.

In contrast to the extensively reported therapeutic activities, far less attention has been paid to the intestinal absorption of the total saponins from Radix Ilicis Pubescentis (in Chinese Mao-Dong-Qing, MDQ). This study aimed to investigate the intestinal absorption characteristics of ilexgenin A (C1), ilexsaponin A1 (C2), ilexsaponin B1 (C3), ilexsaponin B2 (C4), ilexsaponin B3 (DC1), and ilexoside O (DC2) when administrated with the total saponins from MDQ (MDQ-TS). An UPLC method for simultaneous determination of C1, C2, C3, C4, DC1, and DC2 in intestinal outflow perfusate was developed and validated. The absorption characteristics of MDQ-TS were investigated by evaluating the effects of intestinal segments, drug concentration, P-glycoprotein (P-gp) inhibitor (verapomil), endocytosis inhibitor (amantadine) and ethylene diamine tetraacetic acid (EDTA, tight junction modulator) on the intestinal transportation of MDQ-TS by using a single-pass intestinal perfusion (SPIP) rat model, and the influence of co-existing components on the intestinal transport of the six saponins was discussed. The results showed that effective apparent permeability (P_app) of C1, C2, C3, C4, and DC2 administrated in MDQ-TS form had no segment-dependent changes at low and middle dosage levels. C1, C2, C3, D4, DC1, and DC2 administrated in MDQ-TS form all exhibited excellent transmembrane permeability with P_app > 0.12 × 10⁻² cm·min⁻¹. Meanwhile, P_app and effective absorption rate constant (K_a) values for the most saponins showed concentration dependence and saturation characteristics. After combining with P-gp inhibitor of verapamil, P_app of C2, C3, and DC1 in MDQ-TS group was significantly increased up to about 2.3-fold, 1.4-fold, and 3.4-fold, respectively in comparison to that of non-verapamil added group. Verapamil was found to improve the absorption of C2, C3, and DC1, indicating the involvement of an active transport mechanism in the absorption process. Compared with the non-amantadine added group, the absorption of C1, C2, C4, DC1, and DC2 were decreased by 40%, 71%, 31%, 53%, and 100%, respectively. P_app for the six target compounds increased up to about 1.2–2.1-fold in comparison with the non-EDTA added, respectively. The gastrointestinal transport of MDQ-TS could be greatly promoted by EDTA, and inhibited by amantadine, implying that the intestinal absorption of MDQ-TS was by passive diffusion and endocytosis process. Compared with monomer administration group, the intestinal absorption of C3, C4, DC1, and DC2 was significantly improved by co-existing components in MDQ-TS, and the non-absorbable saponins of C4, DC1, and DC2 unexpectedly showed sufficient intestinal permeability with P_app > 0.12 × 10⁻² cm·min⁻¹. This suggested that compounds orally administrated in TCM extract forms displayed unique intestinal absorption characteristics different from those of monomers, and the enhancing intestinal absorption of MDQ-TS reflected a holistic and specific view of traditional Chinese medicines (TCMs). Full article

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15 pages, 3398 KiB

Open AccessCommunication

Biophysical Properties and Antiviral Activities of Measles Fusion Protein Derived Peptide Conjugated with 25-Hydroxycholesterol

by Bárbara Gomes¹

, Nuno C. Santos^1,* and Matteo Porotto^2,3,*

¹ Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal

² Center for Host-Pathogen Interaction, Columbia University Medical Center, 701 W. 168th St., New York, NY 10032, USA

³ Department of Pediatrics, Columbia University Medical Center, 701 W. 168th St., New York, NY 10032, USA

Molecules 2017, 22(11), 1869; https://doi.org/10.3390/molecules22111869 - 31 Oct 2017

Cited by 10 | Viewed by 5569

Abstract

Measles virus (MV) infection is re-emerging, despite the availability of an effective vaccine. The mechanism of MV entry into a target cell relies on coordinated action between the MV hemagglutinin (H) receptor binding protein and the fusion envelope glycoprotein (F) which mediates fusion [...] Read more.

Measles virus (MV) infection is re-emerging, despite the availability of an effective vaccine. The mechanism of MV entry into a target cell relies on coordinated action between the MV hemagglutinin (H) receptor binding protein and the fusion envelope glycoprotein (F) which mediates fusion between the viral and cell membranes. Peptides derived from the C-terminal heptad repeat (HRC) of F can interfere with this process, blocking MV infection. As previously described, biophysical properties of HRC-derived peptides modulate their antiviral potency. In this work, we characterized a MV peptide fusion inhibitor conjugated to 25-hydroxycholesterol (25HC), a cholesterol derivative with intrinsic antiviral activity, and evaluated its interaction with membrane model systems and human blood cells. The peptide (MV Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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12 pages, 2483 KiB

Open AccessArticle

Synthesis and Structure–Activity Relationships of 4-Morpholino-7,8-Dihydro-5H-Thiopyrano[4,3-d]pyrimidine Derivatives Bearing Pyrazoline Scaffold

by Qinqin Wang¹, Xiaojing Li², Chengyu Sun³, Binliang Zhang¹, Pengwu Zheng¹, Wufu Zhu^1,* and Shan Xu^1,*

¹ Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China

² College of Service, Naval Logistics Academy of PLA, Tianjin 300450, China

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

Molecules 2017, 22(11), 1870; https://doi.org/10.3390/molecules22111870 - 31 Oct 2017

Cited by 14 | Viewed by 5137

Abstract

Phosphatidylinositol 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is abnormally active in the growth and proliferation of cancer cells. The inhibition of PI3K kinase can effectively block the conduction of signaling pathways and is an ideal target for drug design. In [...] Read more.

Phosphatidylinositol 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is abnormally active in the growth and proliferation of cancer cells. The inhibition of PI3K kinase can effectively block the conduction of signaling pathways and is an ideal target for drug design. In this paper; two series of 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing pyrazoline moiety (7a–l; 8a–l) were synthesized; and their cytotoxicity in vitro were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method against four human cancer cell lines including A549; PC-3; MCF-7; and HepG2 cell lines. The activity of the most promising compound 8d against PI3Kα kinase was further evaluated. The results indicated that most of the target compounds showed moderate to excellent cytotoxicity and the most promising compound 8d showed excellent cytotoxicity against four cancer cell lines with half maximal inhibitory concentration (IC₅₀) values of 6.02–10.27 μM. In addition; the compound 8d was found to have a moderate inhibitory activity in the PI3Kα enzyme assay. What’s more; the compounds of which the substituents of benzene ring at the C-4 position are electron-withdrawing groups such as substituents (Cl; F; Br) have better activity than the compounds containing the electron donating groups (OCH₃; H). However; the exact action mechanism is not quite clear right now. Further study will be carried out to identify the exact target in near future. Full article

(This article belongs to the Special Issue Pyrazole Derivatives)

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16 pages, 2887 KiB

Open AccessArticle

Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation

by Harold Spedding, Peter Karuso

and Fei Liu^*

Department of Molecular Sciences, Macquarie University, Sydney, NSW 2109, Australia

Molecules 2017, 22(11), 1871; https://doi.org/10.3390/molecules22111871 - 31 Oct 2017

Cited by 1 | Viewed by 4507

Abstract

Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the [...] Read more.

Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 1691 KiB

Open AccessArticle

Practical Synthesis of Chalcone Derivatives and Their Biological Activities

by Jae-Chul Jung¹, Yongnam Lee², Dongguk Min², Mankil Jung^2,* and Seikwan Oh^1,*

¹ Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul 07985, Korea

² Department of Chemistry, Yonsei University, Seoul 03722, Korea

Molecules 2017, 22(11), 1872; https://doi.org/10.3390/molecules22111872 - 1 Nov 2017

Cited by 47 | Viewed by 17774

Abstract

Practical synthesis and biological activities of 4-hydroxy-3-methoxy-2-propene derivatives are described. The novel chalcone derivatives were prepared by acid catalysed one-step condensation of 1,3- or 1,4-diacetylbenzene and 1,3,5-triacetylbenzene with 4-hydroxy-3-methoxybenzaldehyde. They were then evaluated for free radical scavenging activity, suppression of lipopolysaccharides (LPS)-induced NO [...] Read more.

Practical synthesis and biological activities of 4-hydroxy-3-methoxy-2-propene derivatives are described. The novel chalcone derivatives were prepared by acid catalysed one-step condensation of 1,3- or 1,4-diacetylbenzene and 1,3,5-triacetylbenzene with 4-hydroxy-3-methoxybenzaldehyde. They were then evaluated for free radical scavenging activity, suppression of lipopolysaccharides (LPS)-induced NO generation, and anti-excitotoxicity in vitro. It was found that all compounds showed good effects for 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, LPS-induced NO generation, and anti-neurotoxicity. Compounds 6 and 7 were potent suppressor of NO generation with the concentration range 10 µM and especially compound 8 showed very potent anti-inflammatory activity with 1 µM. In addition, the di- and tri-acetylbenzyl derivatives 6, 7, and 8 showed enhanced anti-neurotoxicity activity in cultured cortical neurons. Molecular modelling studies to investigate the chemical structural characteristics required for the enhanced biological activities interestingly revealed that compound 8 has the smallest highest occupied molecular orbital-lowest energy unoccupied molecular orbital (HOMO-LUMO) gap, which signifies easy electron and radical transfer between HOMO and LUMO in model studies. Full article

(This article belongs to the Special Issue Chalcone: A Privileged Structure in Medicinal Chemistry)

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12 pages, 1481 KiB

Open AccessArticle

Acaricidal Activity and Synergistic Effect of Thyme Oil Constituents against Carmine Spider Mite (Tetranychus Cinnabarinus (Boisduval))

by Lipeng Wu^1,2,3, Xin Huo⁴, Xiaolong Zhou^1,3, Duoyong Zhao^1,2,3, Weizhong He^1,2,3, Shenghong Liu^1,3, Hejiang Liu^1,3, Ting Feng^1,3 and Cheng Wang^1,2,3,*

¹ Institute of Quality Standards & Testing Technology for Agro-Products, Xinjiang Academy of Agricultural Sciences, Urumqi 830091, Xinjiang, China

² Laboratory of Quality and Safety Risk Assessment for Agro-Products (Urumqi), Ministry of Agriculture, Urumqi 830091, Xinjiang, China

³ Key Laboratory of Agro-Products Quality and Safety of Xinjiang, Urumqi 830091, Xinjiang, China

⁴ Agro Technical Extension Center of Altay Prefecture, Altay 836500, Xinjiang, China

Molecules 2017, 22(11), 1873; https://doi.org/10.3390/molecules22111873 - 1 Nov 2017

Cited by 39 | Viewed by 6511

Abstract

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme [...] Read more.

Studies examining the use of essential oils as replacements for synthetic insecticides require an understanding of the contribution of each constituent present, interactions among these components, and how they relate to overall toxicity. In the present study, the chemical composition of commercial thyme oil was identified by gas chromatography-mass spectrometry. Thyme oil and blends of its major constituents were tested for their acaricidal activitities against carmine spider mites (Tetranychus cinnabarinus (Boisduval)) using a slide-dip bioassay. Natural thyme oil showed greater toxicity than any single constituent or blend of constituents. Thymol was the most abundant component (34.4%), and also possessed the strongest acaricidal activity compared with other single constituents. When tested individually, four constituents (linalool, terpinene, p-cymene and carvacrol) also had activity, while α-pinene, benzoic acid and ethyl gallate had almost no activity. The toxicity of blends of selected constituents indicated a synergistic effect among the putatively active and inactive constituents, with the presence of all constituents necessary to reach the highest toxicity. The results indicated that thyme oil and some of its major constituents have the potential to be developed into botanical acaricides. Full article

(This article belongs to the Collection Bioactive Compounds)

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9 pages, 1264 KiB

Open AccessArticle

Detection of Rare Somatic GNAS Mutation in McCune-Albright Syndrome Using a Novel Peptide Nucleic Acid Probe in a Single Tube

by Fu-Sung Lo^1,2, Tai-Long Chen³ and Chiuan-Chian Chiou^3,4,5,*

¹ Division of Pediatric Endocrinology & Genetics, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan

² School of Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

³ Molecular Medicine Research Center, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁴ Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

⁵ Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan

Molecules 2017, 22(11), 1874; https://doi.org/10.3390/molecules22111874 - 1 Nov 2017

Cited by 5 | Viewed by 6029

Abstract

McCune-Albright syndrome (MAS) is characterized by the triad of precocious puberty, café au lait pigmentation, and polyostotic fibrous dysplasia (FD) of bone, and is caused by post-zygotic somatic mutations—R201H or R201C—in the guanine nucleotide binding protein, alpha stimulating (GNAS) gene. In the present [...] Read more.

McCune-Albright syndrome (MAS) is characterized by the triad of precocious puberty, café au lait pigmentation, and polyostotic fibrous dysplasia (FD) of bone, and is caused by post-zygotic somatic mutations—R201H or R201C—in the guanine nucleotide binding protein, alpha stimulating (GNAS) gene. In the present study, a novel peptide nucleic acid (PNA) probe with fluorescent labeling was designed to detect trace amounts of somatic mutant GNAS in a single tube reaction. The method was applied to screen GNAS mutations in six patients with MAS/FD. The results showed that the PNA probe assay could detect low abundant mutants in 200-fold excess of wild-type alleles. The GNAS mutation was found in three patients with severe disease (MAS) by using the assay. The other three patients with mild disease (having only FD) showed a wild-type result. This study has provided a simple method to detect trace amounts of GNAS mutants with high sensitivity in large amounts of wild-type DNA. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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13 pages, 6380 KiB

Open AccessArticle

The Complete Amomum kravanh Chloroplast Genome Sequence and Phylogenetic Analysis of the Commelinids

by Mingli Wu^1,2, Qing Li³, Zhigang Hu¹, Xiwen Li^2,* and Shilin Chen^1,2,*

¹ Pharmacy Faculty, Hubei University of Chinese Medicine, Wuhan 430065, Hubei, China

² Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China

³ Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

Molecules 2017, 22(11), 1875; https://doi.org/10.3390/molecules22111875 - 1 Nov 2017

Cited by 51 | Viewed by 6581

Abstract

Amomum kravanh is an important edible and medicinal herb, the dried fruits of which are widely used in traditional herbal medicine as cardamom. We sequenced and analyzed the complete chloroplast (cp) genome of A. kravanh with herbgenomics technologies. The size of the A. [...] Read more.

Amomum kravanh is an important edible and medicinal herb, the dried fruits of which are widely used in traditional herbal medicine as cardamom. We sequenced and analyzed the complete chloroplast (cp) genome of A. kravanh with herbgenomics technologies. The size of the A. kravanh cp genome was 162,766 bp, which consisted of long (LSC; 87,728 bp) and short (SSC; 15,390 bp) single-copy regions, separated by a pair of inverted repeats (IRs; 29,824 bp). The genome encoded 114 unique genes, including 80 protein-coding genes, 30 tRNAs and four rRNAs. A total of 299 simple sequence repeats (SSRs) were identified in the A. kravanh cp genome, which provides an effective method to study species identification and population genetics of the medicinal plant. Moreover, one complement, 12 forward, 12 palindrome and two reverse repeats were detected. Comparative cp genome sequence analysis of four Zingiberaceae species indicated that their intergenic spacers are highly divergent, although the gene order, gene content and genome structure differed only minimally. In particular, there was a remarkable expansion of the IR regions in the A. kravanh cp genome. Phylogenetic analysis strongly supported a sister relationship between A. kravanh and Alpinia zerumbet. This study identified the unique characteristics of the A. kravanh cp genome and might provide valuable information for future studies aiming for Amomum identification, and provide insights into the taxonomy of the commelinids. Full article

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16 pages, 793 KiB

Open AccessArticle

Novel Triazole Hybrids of Betulin: Synthesis and Biological Activity Profile

by Ewa Bębenek^1,*, Maria Jastrzębska^2,3, Monika Kadela-Tomanek¹, Elwira Chrobak¹, Beata Orzechowska⁴, Katarzyna Zwolińska⁴, Małgorzata Latocha⁵, Anna Mertas⁶

, Zenon Czuba⁶ and Stanisław Boryczka¹

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

² Department of Solid State Physics, Institute of Physics, University of Silesia, 4 Uniwersytecka Str., 40-007 Katowice, Poland

³ Silesian Center for Education and Interdisciplinary Research, University of Silesia, 75 Pułku Piechoty 1, 41-500 Chorzów, Poland

⁴ Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Virology, 12 Rudolfa Weigla Str., 53-114 Wrocław, Poland

⁵ Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 8 Jedności Str., 41-200 Sosnowiec

⁶ Department of Microbiology and Immunology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, 19 Jordana Str., 41-808 Zabrze, Poland

Molecules 2017, 22(11), 1876; https://doi.org/10.3390/molecules22111876 - 1 Nov 2017

Cited by 61 | Viewed by 6285

Abstract

Betulin derivatives containing a 1,2,3-triazole ring possess a wide spectrum of biological activities, including antiviral, anticancer, and antibacterial activity. A series of novel triazoles were prepared by the 1,3-dipolar cycloaddition reaction between the alkyne derivatives of betulin and organic azides. The chemical structures [...] Read more.

Betulin derivatives containing a 1,2,3-triazole ring possess a wide spectrum of biological activities, including antiviral, anticancer, and antibacterial activity. A series of novel triazoles were prepared by the 1,3-dipolar cycloaddition reaction between the alkyne derivatives of betulin and organic azides. The chemical structures of the obtained compounds were defined by ¹H and ¹³C NMR, IR, and high-resolution mass spectrometry (HR-MS) analysis. The target triazoles were screened for their antiviral activity against DNA and RNA viruses. The cytotoxic activity of the obtained compounds 5a–k and 6a–h was determined using five human cancer cell lines (T47D, MCF-7, SNB-19, Colo-829, and C-32) by a WST-1 assay. The bistriazole 6b displayed a promising IC₅₀ value (0.05 μM) against the human ductal carcinoma T47D (500-fold higher potency than cisplatin). The microdilution method was applied for an evaluation of the antimicrobial activity of all of the compounds. The triazole 5e containing a 3′-deoxythymidine-5′-yl moiety exhibited antibacterial activity against two gram-negative bacteria vz. Klebsiella pneumoniae and Escherichia coli (minimal inhibitory concentration (MIC) range of 0.95–1.95 μM). Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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15 pages, 4346 KiB

Open AccessArticle

Optimization of the Extraction Conditions for Buddleja officinalis Maxim. Using Response Surface Methodology and Exploration of the Optimum Harvest Time

by Guoyong Xie^†

, Ran Li^†, Yu Han, Yan Zhu, Gang Wu and Minjian Qin^*

¹ Department of Resources Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1877; https://doi.org/10.3390/molecules22111877 - 1 Nov 2017

Cited by 16 | Viewed by 5102

Abstract

The Box-Behnken design was used to evaluate the effects of the methanol concentration (60–100%), liquid to solid ratio (20:1 to 40:1 mL/g) and extraction time (20–40 min) on the yield of 11 constituents from Buddleja officinalis Maxim using ultrasound-assisted extraction. The Derringer’s desirability [...] Read more.

The Box-Behnken design was used to evaluate the effects of the methanol concentration (60–100%), liquid to solid ratio (20:1 to 40:1 mL/g) and extraction time (20–40 min) on the yield of 11 constituents from Buddleja officinalis Maxim using ultrasound-assisted extraction. The Derringer’s desirability function approach showed that the modified optimum extraction conditions were: 76% methanol concentration, 33 min extraction time and a 34:1 mL/g solvent to solid ratio. Under these conditions, the experimentally measured yields of the compounds were in good agreement with the predicted values. An accurate and sensitive method was also established using high-performance liquid chromatography with diode-array detection for the simultaneous determination of the 11 compounds in Buddleja officinalis. The newly developed method was used to determine the amounts of bioactive components in Buddleja officinalis during four different growth stages. According to these results, we recommend that the full blossom stage is the best time for harvesting this plant to obtain the highest yield of crude materials. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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14 pages, 673 KiB

Open AccessArticle

Characterization of Free, Conjugated, and Bound Phenolic Acids in Seven Commonly Consumed Vegetables

by Yuan Gao^1,2, Shuai Ma^1,2, Meng Wang^1,2

and Xiao-Yuan Feng^1,2,*

¹ Beijing Research Center for Agricultural Standards and Testing, No. 9 Middle Road of Shuguanghuayuan, Haidian Dist., Beijing 100097, China

² Risk Assessment Laboratory for Agro-products (Beijing), Ministry of Agriculture, No. 9 Middle Road of Shuguanghuayuan, Haidian Dist., Beijing 100097, China

Molecules 2017, 22(11), 1878; https://doi.org/10.3390/molecules22111878 - 1 Nov 2017

Cited by 64 | Viewed by 5088

Abstract

Phenolic acids are thought to be beneficial for human health and responsible for vegetables’ health-promoting properties. Free, conjugated, and bound phenolic acids of seven commonly consumed vegetables, including kidney bean, cow pea, snow pea, hyacinth bean, green soy bean, soybean sprouts and daylily, [...] Read more.

Phenolic acids are thought to be beneficial for human health and responsible for vegetables’ health-promoting properties. Free, conjugated, and bound phenolic acids of seven commonly consumed vegetables, including kidney bean, cow pea, snow pea, hyacinth bean, green soy bean, soybean sprouts and daylily, from the regions of Beijing, Hangzhou, and Guangzhou, were identified and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Three vegetables, namely green soy bean, soybean sprouts, and daylily (Hemerocallis fulva L.), from the Beijing region contained higher concentrations of total phenolic acids than those from the Hangzhou and Guangzhou regions. The results indicated that the phenolic acid content in the seven vegetables appeared to be species-dependent. The highest content of phenolic acids was found in daylily, followed by green soy bean, while the least amounts were identified in kidney bean and hyacinth bean. Typically, phenolic acids are predominantly found in conjugated forms. Principle component analysis (PCA) revealed some key compounds that differentiated the seven vegetables. Green soy bean, compared to the other six vegetables, was characterized by higher levels of syringic acid, ferulic acid, vanillic acid, and sinapic acid. Other compounds, particularly p-coumaric acid, neochlorogenic acid, and caffeic acid, exhibited significantly higher concentrations in daylily. In addition, p-coumaric acid was the characteristic substance in cow pea. Results from this study can contribute to the development of vegetables with specific phytochemicals and health benefits. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2111 KiB

Open AccessArticle

Influence of Amlodipine Enantiomers on Human Microsomal Cytochromes P450: Stereoselective Time-Dependent Inhibition of CYP3A Enzyme Activity

by Kristyna Krasulova¹, Ondrej Holas²

and Pavel Anzenbacher^1,*

¹ Department of Pharmacology and Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacky University at Olomouc, Hnevotinska 3, 775 15 Olomouc, Czech Republic

² Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic

Molecules 2017, 22(11), 1879; https://doi.org/10.3390/molecules22111879 - 3 Nov 2017

Cited by 17 | Viewed by 7313

Abstract

Amlodipine (AML) is available as a racemate, i.e., a mixture of R- and S-enantiomers. Its inhibitory potency towards nine cytochromes P450 (CYP) was studied to evaluate the drug–drug interactions between the enantiomers. Enzyme inhibition was evaluated using specific CYP substrates in [...] Read more.

Amlodipine (AML) is available as a racemate, i.e., a mixture of R- and S-enantiomers. Its inhibitory potency towards nine cytochromes P450 (CYP) was studied to evaluate the drug–drug interactions between the enantiomers. Enzyme inhibition was evaluated using specific CYP substrates in human liver microsomes. With CYP3A, both enantiomers exhibited reversible and time-dependent inhibition. S-AML was a stronger reversible inhibitor of midazolam hydroxylation: the K_i values of S- and R-AML were 8.95 µM, 14.85 µM, respectively. Computational docking confirmed that the enantiomers interact differently with CYP3A: the binding free energy of S-AML in the active site was greater than that for R-AML (−7.6- vs. −6.7 kcal/mol). Conversely, R-AML exhibited more potent time-dependent inhibition of CYP3A activity (K_I 8.22 µM, K_inact 0.065 min⁻¹) than S-AML (K_I 14.06 µM, K_inact 0.041 min⁻¹). R-AML was also a significantly more potent inhibitor of CYP2C9 (K_i 12.11 µM/S-AML 21.45 µM) and CYP2C19 (K_i 5.97 µM/S-AML 7.22 μM. In conclusion, results indicate that clinical use of S-AML has an advantage not only because of greater pharmacological effect, but also because of fewer side effects and drug–drug interactions with cytochrome P450 substrates due to absence of R-AML. Full article

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12 pages, 444 KiB

Open AccessArticle

Abies Concolor Seeds and Cones as New Source of Essential Oils—Composition and Biological Activity

by Anna Wajs-Bonikowska^1,*

, Łukasz Szoka², Ewa Karna², Anna Wiktorowska-Owczarek³ and Monika Sienkiewicz⁴

¹ Institute of General Food Chemistry, Biotechnology and Food Science, Lodz University of Technology, Stefanowskiego St. 4/10, 90-924 Łódź, Poland

² Department of Medicinal Chemistry, Medical University of Bialystok, Kilińskiego St. 1, 15-089 Białystok, Poland

³ Pharmacology and Toxicology Department, Medical University of Lodz, Żeligowskiego St. 7/9, 90-752 Łódź, Poland

⁴ Department of Allergology and Respiratory Rehabilitation, Medical University of Lodz, Hallera Sq.1, 90-549 Łódź, Poland

Molecules 2017, 22(11), 1880; https://doi.org/10.3390/molecules22111880 - 2 Nov 2017

Cited by 8 | Viewed by 4719

Abstract

The chemical composition, including the enantiomeric excess of the main terpenes, of essential oils from seeds and cones of Abies concolor was studied by chromatographic (GC) and spectroscopic methods (mass spectrometry, nuclear magnetic resonance), leading to the determination of 98 compounds. Essential oils [...] Read more.

The chemical composition, including the enantiomeric excess of the main terpenes, of essential oils from seeds and cones of Abies concolor was studied by chromatographic (GC) and spectroscopic methods (mass spectrometry, nuclear magnetic resonance), leading to the determination of 98 compounds. Essential oils were mainly composed of monoterpene hydrocarbons. The dominant volatiles of seed essential oil were: limonene (47 g/100 g, almost pure levorotary form) and α-pinene (40 g/100 g), while α-pinene (58 g/100 g), sabinene (11 g/100 g), and β-pinene (4.5 g/100 g) were the predominant components of the cone oil. The seed and cone essential oils exhibited mild antibacterial activity, and the MIC ranged from 26 to 30 μL/mL against all of the tested bacterial standard strains: Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, and Klebsiella pneumoniae. The cytotoxic studies have demonstrated that tested essential oils were cytotoxic to human skin fibroblasts and human microvascular endothelial cells at concentrations much lower than the MIC. The essential oils from A. concolor seeds and cones had no toxic effect on human skin fibroblasts and human microvascular endothelial cells, when added to the cells at a low concentration (0–0.075 μL/mL) and (0–1.0 μL/mL), respectively, and cultured for 24 h. Full article

(This article belongs to the Section Natural Products Chemistry)

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39 pages, 12133 KiB

Open AccessReview

Peroxides with Anthelmintic, Antiprotozoal, Fungicidal and Antiviral Bioactivity: Properties, Synthesis and Reactions

by Vera A. Vil’^1,2,3

, Ivan A. Yaremenko^1,2,3, Alexey I. Ilovaisky¹ and Alexander O. Terent’ev^1,2,3,*

¹ N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prospekt, 119991 Moscow, Russia

² Faculty of Chemical and Pharmaceutical Technology and Biomedical Products, D. I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Square, 125047 Moscow, Russia

³ All-Russian Research Institute for Phytopathology, B. Vyazyomy, 143050 Moscow, Russia

Molecules 2017, 22(11), 1881; https://doi.org/10.3390/molecules22111881 - 2 Nov 2017

Cited by 70 | Viewed by 11759

Abstract

The biological activity of organic peroxides is usually associated with the antimalarial properties of artemisinin and its derivatives. However, the analysis of published data indicates that organic peroxides exhibit a variety of biological activity, which is still being given insufficient attention. In the [...] Read more.

The biological activity of organic peroxides is usually associated with the antimalarial properties of artemisinin and its derivatives. However, the analysis of published data indicates that organic peroxides exhibit a variety of biological activity, which is still being given insufficient attention. In the present review, we deal with natural, semi-synthetic and synthetic peroxides exhibiting anthelmintic, antiprotozoal, fungicidal, antiviral and other activities that have not been described in detail earlier. The review is mainly concerned with the development of methods for the synthesis of biologically active natural peroxides, as well as its isolation from natural sources and the modification of natural peroxides. In addition, much attention is paid to the substantially cheaper biologically active synthetic peroxides. The present review summarizes 217 publications mainly from 2000 onwards. Full article

(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)

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22 pages, 6014 KiB

Open AccessReview

Recent Advances in the Synthesis of Spiroheterocycles via N-Heterocyclic Carbene Organocatalysis

by Yue Liu^1,†

, Xiang Zhang^1,2,4,†, Rong Zeng¹, Ying Zhang³, Qing-Song Dai¹, Hai-Jun Leng¹, Xiao-Jun Gou¹ and Jun-Long Li^1,2,*

¹ Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China

² Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China

³ College of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China

⁴ University of Chinese Academy of Sciences, Beijing 100049, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1882; https://doi.org/10.3390/molecules22111882 - 8 Nov 2017

Cited by 43 | Viewed by 8329

Abstract

Spiroheterocycles are regarded as a privileged framework because of their wide distribution in various natural products and synthetic molecules and promising bioactivities. This review focuses on the recent advances in the synthesis of spiroheterocycles by using the strategy of N-heterocyclic carbene (NHC) [...] Read more.

Spiroheterocycles are regarded as a privileged framework because of their wide distribution in various natural products and synthetic molecules and promising bioactivities. This review focuses on the recent advances in the synthesis of spiroheterocycles by using the strategy of N-heterocyclic carbene (NHC) organocatalysis, and is organized based on the stereoselectivity and the reactive intermediates. According to the stereochemistry, this review was divided into two main parts, covering racemic and enantioselective versions. In each part, we firstly describe the synthetic transformations using nucleophilic Breslow intermediates, and then discuss the reactions that employ electrophilic acylazolium or radical cation intermediates. With those distinct catalytic activation modes of NHC organocatlysis, we expect this synthetic protocol will possibly produce new molecules with structural novelty and complexity, which may warrant further research in the field of drug discovery. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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15 pages, 1343 KiB

Open AccessArticle

Anti-Inflammatory Effect of Malva sylvestris, Sida cordifolia, and Pelargonium graveolens Is Related to Inhibition of Prostanoid Production

by Cleverson Antonio Ferreira Martins¹, Michel Leandro Campos¹, Ana Carolina Irioda², Dile Pontarolo Stremel¹, Angela Cristina Leal Badaró Trindade¹ and Roberto Pontarolo^1,*

¹ Department of Pharmacy, Universidade Federal do Paraná, 632 Lothário Meissner Avenue, Curitiba 80210-170, Brazil

² Department of Pharmacy, Pelé Pequeno Príncipe Research Institute, 1632 Silva Jardim Avenue, Curitiba 80250-060, Brazil

Molecules 2017, 22(11), 1883; https://doi.org/10.3390/molecules22111883 - 3 Nov 2017

Cited by 31 | Viewed by 8010

Abstract

The ability of plant extracts and preparations to reduce inflammation has been proven by different means in experimental models. Since inflammation enhances the release of specific mediators, inhibition of their production can be used to investigate the anti-inflammatory effect of plants widely used [...] Read more.

The ability of plant extracts and preparations to reduce inflammation has been proven by different means in experimental models. Since inflammation enhances the release of specific mediators, inhibition of their production can be used to investigate the anti-inflammatory effect of plants widely used in folk medicine for this purpose. The study was performed for leaves and flowers of Malva sylvestris, and leaves of Sida cordifolia and Pelargonium graveolens. These are three plant species known in Brazil as Malva. The anti-inflammatory activity of extracts and fractions (hexane, chloroform, ethyl acetate, and residual) was evaluated by quantitation of prostaglandins (PG) PGE₂, PGD₂, PGF_2α, and thromboxane B₂ (the stable nonenzymatic product of TXA₂) concentration in the supernatant of lipopolysaccharide (LPS)- induced RAW 264.7 cells. Inhibition of anti-inflammatory mediator release was observed for plants mainly in the crude extract, ethyl acetate fraction, and residual fraction. The results suggest superior activity of S. cordifolia, leading to significantly lower values of all mediators after treatment with its residual fraction, even at the lower concentration tested (10 μg/mL). M. sylvestris and P. graveolens showed similar results, such as the reduction of all mediators after treatment, with leaf crude extracts (50 μg/mL). These results suggest that the three species known as Malva have anti-inflammatory properties, S. cordifolia being the most potent. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 11078 KiB

Open AccessArticle

Fast Extraction and Detection of 4-Methylimidazole in Soy Sauce Using Magnetic Molecularly Imprinted Polymer by HPLC

by Zufei Feng¹, Yan Lu¹, Yingjuan Zhao¹ and Helin Ye^2,*

¹ Department of Applied Chemistry, School of Science, Xi’an University of Technology, Xi’an 710061, China

² School of Chemistry and Environmental Science, Lanzhou City University, Lanzhou 730070, China

Molecules 2017, 22(11), 1885; https://doi.org/10.3390/molecules22111885 - 2 Nov 2017

Cited by 7 | Viewed by 4913

Abstract

On the basis of magnetic molecularly imprinted polymer (MMIP) solid-phase extraction coupled with high performance liquid chromatography, we established a new method for the determination of the 4-methylimidazole (4-MEI) in soy sauce. Scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray diffraction (XRD) [...] Read more.

On the basis of magnetic molecularly imprinted polymer (MMIP) solid-phase extraction coupled with high performance liquid chromatography, we established a new method for the determination of the 4-methylimidazole (4-MEI) in soy sauce. Scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) were used to characterize the synthesized MMIPs. To evaluate the polymers, batch rebinding experiments were carried out. The binding strength and capacity were determined from the derived Freundlich isotherm (FI) equation. The selective recognition capability of MMIPs was investigated with a reference compound and a structurally similar compound. As a selective pre-concentration sorbents for 4-methylimidazole in soy sauce, the MMIPs showed a satisfied recoveries rate of spiked samples, ranged from 97% to 105%. As a result, the prepared MMIPs could be applied to selectively pre-concentrate and determine 4-methylimidazole in soy sauce samples. Full article

(This article belongs to the Special Issue Synthesis and Applications of Molecularly Imprinted Polymers)

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10 pages, 3393 KiB

Open AccessArticle

Atractylenolide II Inhibits Proliferation, Motility and Induces Apoptosis in Human Gastric Carcinoma Cell Lines HGC-27 and AGS

by Shuang Tian^* and Hongdan Yu

Department of Cell Biology, Jinzhou Medical University, Jinzhou 121000, China

Molecules 2017, 22(11), 1886; https://doi.org/10.3390/molecules22111886 - 3 Nov 2017

Cited by 46 | Viewed by 5130

Abstract

Atractylenolide II (AT-II) exhibits several biological and pharmacological functions, especially anti-cancer activity as the major sesquiterpene lactones isolated from Atractylodes macrocephala (also named Baizhu in Chinese). However, the effects and mechanisms of AT-II on human gastric cancer remain unclear. Cell Counting Kit-8 (CCK-8) [...] Read more.

Atractylenolide II (AT-II) exhibits several biological and pharmacological functions, especially anti-cancer activity as the major sesquiterpene lactones isolated from Atractylodes macrocephala (also named Baizhu in Chinese). However, the effects and mechanisms of AT-II on human gastric cancer remain unclear. Cell Counting Kit-8 (CCK-8) assay, morphological changes, flow cytometry, wound healing assay and Western blot analysis were used to investigate the effects of AT-II on cell proliferation, apoptosis and motility of human gastric carcinoma cell lines HGC-27 and AGS. Our results indicated that AT-II could significantly inhibit cell proliferation, motility and induce apoptosis in a dose and time-dependent manner. Western blot analysis showed that the expression level of Bax was upregulated and the expression levels of B-cell lymphoma-2 (Bcl-2), phosphorylated-protein kinase B (p-Akt) and phosphorylated-ERK (p-ERK) were downregulated compared to control group. In conclusion, the findings suggested that AT-II exerted significant anti-tumor effects on gastric carcinoma cells by modulating Akt/ERK signaling pathway, which might shed light on therapy of gastric carcinoma. Full article

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16 pages, 1605 KiB

Open AccessArticle

Chemical Composition of Herbal Macerates and Corresponding Commercial Essential Oils and Their Effect on Bacteria Escherichia coli

by Marietta Białoń^1,*, Teresa Krzyśko-Łupicka², Agnieszka Pik¹ and Piotr P. Wieczorek¹

¹ Faculty of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland

² Independent Department of Biotechnology and Molecular Biology, Faculty of Natural and Technical Science, University of Opole, Kominka 6A, 45-035 Opole, Poland

Molecules 2017, 22(11), 1887; https://doi.org/10.3390/molecules22111887 - 10 Nov 2017

Cited by 11 | Viewed by 6136

Abstract

This study addresses the chemical composition of some commercial essential oils (clove, juniper, oregano, and marjoram oils), as well as appropriate herbal extracts obtained in the process of cold maceration and their biological activity against selected Escherichia coli strains: E. coli ATTC 25922, [...] Read more.

This study addresses the chemical composition of some commercial essential oils (clove, juniper, oregano, and marjoram oils), as well as appropriate herbal extracts obtained in the process of cold maceration and their biological activity against selected Escherichia coli strains: E. coli ATTC 25922, E. coli ATTC 10536, and E. coli 127 isolated from poultry waste. On the basis of the gas chromatography-mass spectrometry (GCMS) analysis, it was found that the commercial essential oils revealed considerable differences in terms of the composition and diversity of terpenes, terpenoids and sesquiterpenes as compared with the extracts obtained from plant material. The commercial clove, oregano, and marjoram oils showed antibacterial properties against all the tested strains of E. coli. However, these strains were not sensitive to essential oils obtained from the plant material in the process of maceration. The tested strains of E. coli show a high sensitivity, mainly against monoterpenes (α-pinene, β-pinene, α,β,γ-terpinene, limonene) and some terpenoids (thymol, carvacrol). The commercial juniper oil contained mainly monoterpenes and monoterpenoids, while the extracts contained lower amounts of monoterpenes and high amounts of sesquiterpenes—the anti-microbiotic properties of the juniper herbal extract seem to be caused by the synergistic activity of mono- and sesquiterpenes. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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13 pages, 1051 KiB

Open AccessArticle

A Rapid and Simple TLC-Densitometric Method for Assay of Clobetasol Propionate in Topical Solution

by Malgorzata Dolowy^1,*

, Violetta Kozik², Andrzej Bak²

, Josef Jampilek^3,*

, Krzysztof Barbusinski⁴, Maciej Thomas⁵

and Alina Pyka-Pajak¹

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

² Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia

⁴ Institute of Water and Wastewater Engineering, Silesian University of Technology, Konarskiego 18, 44-100 Gliwice, Poland

⁵ Chemiqua Company, Skawinska 25/1, 31-066 Krakow, Poland

Molecules 2017, 22(11), 1888; https://doi.org/10.3390/molecules22111888 - 3 Nov 2017

Cited by 10 | Viewed by 5728

Abstract

A rapid, simple to use and low-cost thin-layer chromatographic procedure in normal phase system with densitometric detection at 246 nm was carefully validated according to the International Conference on Harmonisation (ICH) guidelines for assay of clobetasol propionate in topical solution containing clobetasol propionate [...] Read more.

A rapid, simple to use and low-cost thin-layer chromatographic procedure in normal phase system with densitometric detection at 246 nm was carefully validated according to the International Conference on Harmonisation (ICH) guidelines for assay of clobetasol propionate in topical solution containing clobetasol propionate in quantity 0.50 mg/mL. The adopted thin-layer chromatographic (TLC)-densitometric procedure could effectively separate clobetasol propionate from its related compound, namely clobetasol. It is linear for clobetasol propionate in the range of 0.188 ÷ 5 µg/spot. The limit of detection (LOD) and limit of quantification (LOQ) value is 0.061 and 0.186 µg/spot, respectively. Accuracy of proposed procedure was evaluated by recovery test. The mean recovery of studied clobetasol propionate ranges from 98.7 to 101.0%. The coefficient of variation (CV, %) obtained during intra-day and inter-day studies, which was less than 2% (0.40 ÷ 1.17%), confirms the precision of described method. The assay value of clobetasol propionate is consistent with the pharmacopoeial requirements. In conclusion, it can be suitable as a simple and economic procedure for routine quality control laboratories of clobetasol propionate in topical solution. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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11 pages, 832 KiB

Open AccessArticle

Synthesis and Antibacterial Activity of Benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide Derivatives

by Jatinder P. Bassin^1,*

, Michelle J. Botha¹, Rajesh Garikipati¹, Madhu Goyal^1,*, Lee Martin²

and Amit Shah¹

¹ School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK

² School of Science and Technology, Nottingham Trent University, Clifton Lane, Clifton, Nottingham NG11 8NS, UK

Molecules 2017, 22(11), 1889; https://doi.org/10.3390/molecules22111889 - 4 Nov 2017

Cited by 9 | Viewed by 5050

Abstract

Using a routine procedure, a number of derivatives of the benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide ring system have been synthesized from readily available starting materials. A series of chalcones were synthesized, which were subsequently reacted with chlorosulfonic acid to generate chalcone sulfonyl chlorides. The chalcone [...] Read more.

Using a routine procedure, a number of derivatives of the benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide ring system have been synthesized from readily available starting materials. A series of chalcones were synthesized, which were subsequently reacted with chlorosulfonic acid to generate chalcone sulfonyl chlorides. The chalcone sulfonyl chlorides were then treated with bromine to generate dibromo chalcone sulfonyl chlorides. These were subsequently reacted with 1,2-diaminopropane and 2-methyl-1,2-diaminopropane in boiling ethanol resulting in compounds 2–10 and 11–19 respectively, in 12–80% yields. The products were characterized by spectral analysis and the definitive structure of compound 11 was determined by X-ray crystallography. The synthesized compounds were screened for potential antibacterial properties against Bacillus subtilis, Escherichia coli, Proteus vulgaris and Staphylococcus aureus. Full article

(This article belongs to the Collection Antibiotics & Superbugs: New Strategies to Combat Antimicrobial Resistance)

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1 pages, 157 KiB

Open AccessErratum

Erratum: Carrasco-Sánchez, V.; et al. Removal of 4-Ethylphenol and 4-Ethylguaiacol with Polyaniline-Based Compounds in Wine-Like Model Solutions and Red Wine. Molecules 2015, 20(8), 14312–14325

by Verónica Carrasco-Sánchez¹, Amalraj John², Adolfo Marican^2,3, Leonardo S. Santos^2,3

and V. Felipe Laurie^1,3,*

¹ School of Agricultural Sciences, Universidad de Talca, Talca 3460000, Chile

² Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Universidad de Talca, Talca 3460000, Chile

³ Nanobiotechnology Division at Universidad de Talca, Fraunhofer Chile Research Foundation—Center for Systems Biotechnology, FCR-CSB, Talca 3460000, Chile

Molecules 2017, 22(11), 1890; https://doi.org/10.3390/molecules22111890 - 7 Nov 2017

Cited by 1 | Viewed by 2522

Abstract

n/a Full article

15 pages, 2023 KiB

Open AccessArticle

Glypre: In Silico Prediction of Protein Glycation Sites by Fusing Multiple Features and Support Vector Machine

by Xiaowei Zhao^1,2, Xiaosa Zhao¹, Lingling Bao¹, Yonggang Zhang², Jiangyan Dai³ and Minghao Yin^1,*

¹ School of Computer Science and Information Technology, Northeast Normal University, Changchun 130117, China

² Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun 130012, China

³ School of Computer Engineering, Weifang University, Weifang 261061, China

Molecules 2017, 22(11), 1891; https://doi.org/10.3390/molecules22111891 - 3 Nov 2017

Cited by 17 | Viewed by 5351

Abstract

Glycation is a non-enzymatic process occurring inside or outside the host body by attaching a sugar molecule to a protein or lipid molecule. It is an important form of post-translational modification (PTM), which impairs the function and changes the characteristics of the proteins [...] Read more.

Glycation is a non-enzymatic process occurring inside or outside the host body by attaching a sugar molecule to a protein or lipid molecule. It is an important form of post-translational modification (PTM), which impairs the function and changes the characteristics of the proteins so that the identification of the glycation sites may provide some useful guidelines to understand various biological functions of proteins. In this study, we proposed an accurate prediction tool, named Glypre, for lysine glycation. Firstly, we used multiple informative features to encode the peptides. These features included the position scoring function, secondary structure, AAindex, and the composition of k-spaced amino acid pairs. Secondly, the distribution of distinctive features of the residues surrounding the glycation and non-glycation sites was statistically analysed. Thirdly, based on the distribution of these features, we developed a new predictor by using different optimal window sizes for different properties and a two-step feature selection method, which utilized the maximum relevance minimum redundancy method followed by a greedy feature selection procedure. The performance of Glypre was measured with a sensitivity of 57.47%, a specificity of 90.78%, an accuracy of 79.68%, area under the receiver-operating characteristic (ROC) curve (AUC) of 0.86, and a Matthews’s correlation coefficient (MCC) of 0.52 by 10-fold cross-validation. The detailed analysis results showed that our predictor may play a complementary role to other existing methods for identifying protein lysine glycation. The source code and datasets of the Glypre are available in the Supplementary File. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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12 pages, 5640 KiB

Open AccessArticle

Continuous Preparation of Hollow Polymeric Nanocapsules Using Self-Assembly and a Photo-Crosslinking Process of an Amphiphilic Block Copolymer

by Xuan Don Nguyen¹

, Hyeong Jin Jeon¹

, Van Tien Nguyen¹, Dong Hyeok Park¹, Taeheon Lee², Hyun-jong Paik^2,*, June Huh³ and Jeung Sang Go^1,*

¹ School of Mechanical Engineering, Pusan National University, 2, Busandaehak-ro 63 beon-gil, Geumjeong-gu, Busan 46241, Korea

² Department of Polymer Science & Engineering, Pusan National University, 2, Busandaehak-ro 63 beon-gil, Geumjeong-gu, Busan 46241, Korea

³ Department of Chemical & Biological Engineering, College of Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 02841, Korea

Molecules 2017, 22(11), 1892; https://doi.org/10.3390/molecules22111892 - 3 Nov 2017

Cited by 2 | Viewed by 4854

Abstract

This paper presents a fabrication method of hollow polymeric nanocapsules (HPNCs). The HPNCs were examined to reduce light trapping in an organic light emitting diodes (OLED) device by increasing the refractive index contrast. They were continuously fabricated by the sequential process of self-assembly [...] Read more.

This paper presents a fabrication method of hollow polymeric nanocapsules (HPNCs). The HPNCs were examined to reduce light trapping in an organic light emitting diodes (OLED) device by increasing the refractive index contrast. They were continuously fabricated by the sequential process of self-assembly and photo-crosslinking of an amphiphilic block copolymer of SBR-b-PEGMA, poly(styrene-r-butadiene)-b-poly(poly(ethylene glycol) methyl ether methacrylate) in a flow-focusing microfluidic device. After the photo-crosslinking process, the produced HPNCs have a higher resistance to water and organic solvents, which is applicable to the fabrication process of optical devices. The morphology and hollow structure of the produced nanocapsules were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). Also, their size control was examined by varying the ratio of inlet flow rates and the morphological difference was studied by changing the polymer concentration. The size was measured by dynamic light scattering (DLS). The refractive index of the layer with and without the HPNCs was measured, and a lower refractive index was obtained in the HPNCs-dispersed layer. In future work, the light extraction efficiency of the HPNCs-dispersed OLED will be examined. Full article

(This article belongs to the Special Issue Supramolecular Chemistry and Self-Assembly: Themed Issue in Honor of Professor Itamar Willner on the Occasion of His 70th Birthday)

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16 pages, 1580 KiB

Open AccessArticle

Structural and Functional Properties Changes of β-Conglycinin Exposed to Hydroxyl Radical-Generating Systems

by Jing Xu¹, Zijing Chen¹, Dong Han¹, Yangyang Li¹, Xiaotong Sun¹, Zhongjiang Wang^2,* and Hua Jin^1,*

¹ College of Science, Northeast Agricultural University, Harbin 150030, Heilongjiang, China, xujing@neau.edu.cn (J.X.)

² College of Food Science, Northeast Agricultural University, Harbin 150030, Heilongjiang, China

Molecules 2017, 22(11), 1893; https://doi.org/10.3390/molecules22111893 - 3 Nov 2017

Cited by 28 | Viewed by 4806

Abstract

The objective of the present study was to examine the structural and functional changes of β-conglycinin exposed to oxidizing radicals produced by FeCl₃/H₂O₂/ascorbic acid hydroxyl radical-generating system (HRGS) for 3 h at room temperature. Increasing H₂ [...] Read more.

The objective of the present study was to examine the structural and functional changes of β-conglycinin exposed to oxidizing radicals produced by FeCl₃/H₂O₂/ascorbic acid hydroxyl radical-generating system (HRGS) for 3 h at room temperature. Increasing H₂O₂ concentrations resulted in a loss of histidine residues, lysine residues, and available lysine, which was accompanied by the formation of protein carbonyls and disulphide bonds (p < 0.05). Changes in secondary structure, surface hydrophobicity, and intrinsic fluorescence indicated that hydroxyl radicals had induced protein unfolding and conformational alterations. Results from SDS-PAGE implied that a small amount of protein cross-linkages produced by oxidative incubation. The emulsifying properties of β-conglycinin were gradually improved with the increasing extent of oxidation. The structural changes above contributed to the reduction of potential allergenicity of β-conglycinin, as verified by specific ELISA analysis. These results suggest that moderate oxidation could partially improve the protein functional properties and reduced the potential allergy of protein, providing guidance for effective use of moderately oxidized soy protein in the industry. Full article

(This article belongs to the Collection Bioactive Compounds)

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15 pages, 26820 KiB

Open AccessArticle

Microwave-Assisted Extraction of Cannabinoids in Hemp Nut Using Response Surface Methodology: Optimization and Comparative Study

by Chih-Wei Chang¹

, Ching-Chi Yen¹, Ming-Tsang Wu², Mei-Chich Hsu^3,4 and Yu-Tse Wu^1,4,*

¹ School of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

² Chinese Medicine Department, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi City 60002, Taiwan

³ Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

⁴ Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan

Molecules 2017, 22(11), 1894; https://doi.org/10.3390/molecules22111894 - 3 Nov 2017

Cited by 48 | Viewed by 10242

Abstract

Hemp nut is commonly incorporated into several food preparations; however, most countries set regulations for hemp products according to their cannabinoid content. In this study, we have developed an efficient microwave-assisted extraction (MAE) method for cannabinoids (i.e., Δ9-tetrahydrocannabinol, cannabidiol, and cannabinol) in hemp [...] Read more.

Hemp nut is commonly incorporated into several food preparations; however, most countries set regulations for hemp products according to their cannabinoid content. In this study, we have developed an efficient microwave-assisted extraction (MAE) method for cannabinoids (i.e., Δ9-tetrahydrocannabinol, cannabidiol, and cannabinol) in hemp nut. Optimization of the MAE procedure was conducted through single factor experiments and response surface methodology (RSM). A comparative study was also conducted to determine the differences in the extraction yields and morphology of hemp nut between MAE and reference extraction methods, namely heat reflux extraction (HRE), Soxhlet extraction (SE), supercritical fluid extraction (SFE), and ultrasound-assisted extraction (UAE). Among the independent variables in RSM, the temperature was the most significant parameter. The optimal conditions of MAE were as follows: extraction solvent of methanol, microwave power of 375 W, temperature of 109 °C, and extraction time of 30 min. Compared with reference extraction methods, MAE achieved the highest extraction yields of total cannabinoids in hemp nut (6.09 μg/g for MAE; 4.15 μg/g for HRE; 5.81 μg/g for SE; 3.61 μg/g for SFE; 3.73 μg/g for UAE) with the least solvent consumption and shortest time. Morphological observations showed that substantial cell rupturing occurred in the microstructure of hemp nut after MAE, indicating enhanced dissolution of the target compounds during the extraction process. The MAE method is thus a rapid, economic, and environmentally friendly extraction method that is both effective and practical for industrial applications. Full article

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12 pages, 1108 KiB

Open AccessArticle

Synthesis, Single Crystal X-ray Analysis, and Antifungal Profiling of Certain New Oximino Ethers Bearing Imidazole Nuclei

by Reem I. Al-Wabli^1,*, Alwah R. Al-Ghamdi¹, Hazem A. Ghabbour^1,2

, Mohamed H. Al-Agamy^3,4

and Mohamed I. Attia^1,5,*

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

² Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt

³ Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

⁴ Microbiology and Immunology Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt

⁵ Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), El Bohooth Street, Dokki, Giza 12622, Egypt

Molecules 2017, 22(11), 1895; https://doi.org/10.3390/molecules22111895 - 3 Nov 2017

Cited by 4 | Viewed by 4108

Abstract

Fungal infections threaten human health, particularly in immune-compromised patients worldwide. Although there are a large number of antifungal agents available, the desired clinical attributes for the treatment of fungal infections have not yet been achieved. Azoles are the mainstay class of the clinically [...] Read more.

Fungal infections threaten human health, particularly in immune-compromised patients worldwide. Although there are a large number of antifungal agents available, the desired clinical attributes for the treatment of fungal infections have not yet been achieved. Azoles are the mainstay class of the clinically used antifungal agents. In the current study, the synthesis, spectroscopic characterization, and antifungal activity of certain new oximino ethers Va–n bearing imidazole nuclei are reported. The (E)-configuration of the imine double bond of the synthesized compounds Va–n has been confirmed via single crystal X-ray analysis of compound Vi as a representative example of this class of compounds. The molecular structure of compound Vi was crystallized in the monoclinic, P2₁/c, a = 18.7879(14) Å, b = 5.8944(4) Å, c = 16.7621(12) Å, β = 93.063(3)°, V = 1855.5(2) Å³, Z = 4. The in vitro antifungal activity of the synthesized compounds Va–n were evaluated using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against different fungal strains. Compound Ve manifested anti-Candida albicans activity with an MIC value of 0.050 µmol/mL, being almost equipotent with the reference antifungal drug fluconazole (FLC),while compounds Vi and Vn are the most active congeners against Candida parapsilosis, being equipotent and about twenty-three times more potent than FLC with an MIC value of 0.002 µmol/mL. The results of the current report might support the development of new potent and safer antifungal azoles. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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16 pages, 4483 KiB

Open AccessArticle

PSN-PC: A Novel Antimicrobial and Anti-Biofilm Peptide from the Skin Secretion of Phyllomedusa-camba with Cytotoxicity on Human Lung Cancer Cell

by Xianhui Wu^1,2, Jinhuo Pan^1,*, Yue Wu², Xinping Xi², Chengbang Ma², Lei Wang², Mei Zhou² and Tianbao Chen²

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210000, China

² Natural Drug Discovery Group, School of Pharmacy, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK

Molecules 2017, 22(11), 1896; https://doi.org/10.3390/molecules22111896 - 7 Nov 2017

Cited by 23 | Viewed by 5686

Abstract

Peptides derived from amphibian skin secretion are promising drug prototypes for combating widespread infection. In this study, a novel peptide belonging to the phylloseptin family of antimicrobial peptides was isolated from the skin secretion of the Phyllomedusa camba, namely phylloseptin-PC (PSN-PC). The [...] Read more.

Peptides derived from amphibian skin secretion are promising drug prototypes for combating widespread infection. In this study, a novel peptide belonging to the phylloseptin family of antimicrobial peptides was isolated from the skin secretion of the Phyllomedusa camba, namely phylloseptin-PC (PSN-PC). The biosynthetic precursor was obtained by molecular cloning and the mature peptide sequence was confirmed through tandem mass spectrometry (MS/MS) fragmentation sequencing in the skin secretion. The synthetic replicate exhibited a broad spectrum antimicrobial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans at concentrations of 2, 2, 8, 32 and 2 µM, respectively. It also showed the capability of eliminating S. aureus biofilm with a minimal biofilm eradication concentration of 8 µM. The haemolysis of this peptide was not significant at low concentrations but had a considerable increase at high concentrations. Additionally, this peptide showed an anti-proliferation effect on the non-small cell lung cancer cell line (NCI-H157), with low cytotoxicity on the human microvascular endothelial cell line (HMEC-1). The discovery of the novel peptide may provide useful clues for new drug discoveries. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Peptidomimetics)

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14 pages, 2196 KiB

Open AccessArticle

Total Synthesis and Metabolic Stability of Hispidulin and Its d-Labelled Derivative

by Liang-Chieh Chen^1,2

, Kai-Cheng Hsu³, Lih-Chu Chiou^4,5

, Hui-Ju Tseng^1,6 and Wei-Jan Huang^1,6,7,8,*

¹ Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan

² School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan

³ Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan

⁴ Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 110, Taiwan

⁵ Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 100, Taiwan

⁶ Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan

⁷ Program for the Clinical Drug Discovery from Botanical Herbs, Taipei 110, Taiwan

⁸ School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan

Molecules 2017, 22(11), 1897; https://doi.org/10.3390/molecules22111897 - 4 Nov 2017

Cited by 12 | Viewed by 6753

Abstract

Hispidulin is a naturally occurring flavone known to have various Central nervous system (CNS) activities. Proposed synthetic approaches to synthesizing hispidulin have proven unsatisfactory due to their low feasibility and poor overall yields. To solve these problems, this study developed a novel scheme [...] Read more.

Hispidulin is a naturally occurring flavone known to have various Central nervous system (CNS) activities. Proposed synthetic approaches to synthesizing hispidulin have proven unsatisfactory due to their low feasibility and poor overall yields. To solve these problems, this study developed a novel scheme for synthesizing hispidulin, which had an improved overall yield as well as more concise reaction steps compared to previous methods reported. Additionally, using the same synthetic strategy, d-labelled hispidulin was synthesized to investigate its metabolic stability against human liver microsome. This work may produce new chemical entities for enriching the library of hispidulin-derived compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2051 KiB

Open AccessArticle

Antibacterial Activity of the Non-Cytotoxic Peptide (p-BthTX-I)₂ and Its Serum Degradation Product against Multidrug-Resistant Bacteria

by Norival A. Santos-Filho^1,*

, Rafaela S. Fernandes², Bruna F. Sgardioli², Matheus A. S. Ramos³

, Julia P. Piccoli¹, Ilana L. B. C. Camargo², Tais M. Bauab³

and Eduardo M. Cilli^1,*

¹ Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-060, Brazil

² Instituto de Física de São Carlos, USP—Universidade de São Paulo, São Carlos-SP 13563-120, Brazil

³ Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Araraquara-SP 14800-903, Brazil

Molecules 2017, 22(11), 1898; https://doi.org/10.3390/molecules22111898 - 4 Nov 2017

Cited by 26 | Viewed by 5580

Abstract

Antimicrobial peptides can be used systemically, however, their susceptibility to proteases is a major obstacle in peptide-based therapeutic development. In the present study, the serum stability of p-BthTX-I (KKYRYHLKPFCKK) and (p-BthTX-I)₂, a p-BthTX-I disulfide-linked dimer, were analyzed by mass spectrometry and [...] Read more.

Antimicrobial peptides can be used systemically, however, their susceptibility to proteases is a major obstacle in peptide-based therapeutic development. In the present study, the serum stability of p-BthTX-I (KKYRYHLKPFCKK) and (p-BthTX-I)₂, a p-BthTX-I disulfide-linked dimer, were analyzed by mass spectrometry and analytical high-performance liquid chromatography (HPLC). Antimicrobial activities were assessed by determining their minimum inhibitory concentrations (MIC) using cation-adjusted Mueller–Hinton broth. Furthermore, biofilm eradication and time-kill kinetics were performed. Our results showed that p-BthTX-I and (p-BthTX-I)₂ were completely degraded after 25 min. Mass spectrometry showed that the primary degradation product was a peptide that had lost four lysine residues on its C-terminus region (des-Lys¹²/Lys¹³-(p-BthTX-I)₂), which was stable after 24 h of incubation. The antibacterial activities of the peptides p-BthTX-I, (p-BthTX-I)₂, and des-Lys¹²/Lys¹³-(p-BthTX-I)₂ were evaluated against a variety of bacteria, including multidrug-resistant strains. Des-Lys¹²/Lys¹³-(p-BthTX-I)₂ and (p-BthTX-I)₂ degraded Staphylococcus epidermidis biofilms. Additionally, both the peptides exhibited bactericidal activities against planktonic S. epidermidis in time-kill assays. The emergence of bacterial resistance to a variety of antibiotics used in clinics is the ultimate challenge for microbial infection control. Therefore, our results demonstrated that both peptides analyzed and the product of proteolysis obtained from (p-BthTX-I)₂ are promising prototypes as novel drugs to treat multidrug-resistant bacterial infections. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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14 pages, 1804 KiB

Open AccessArticle

HPLC Analysis and Biochemical Characterization of LOX from Eschscholtzia californica Cham.

by Renáta Kollárová^1,*, Ivana Holková¹, Drahomíra Rauová^2,3, Barbora Bálintová¹, Peter Mikuš^2,3 and Marek Obložinský¹

¹ Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, 832 32 Bratislava, Slovak Republic

² Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovak Republic

³ Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovak Republic

Molecules 2017, 22(11), 1899; https://doi.org/10.3390/molecules22111899 - 4 Nov 2017

Cited by 4 | Viewed by 5295

Abstract

Background: Plant lipoxygenases (LOXs, EC 1.13.11.12) are involved in lipid degradation, regulation of growth and development, senescence, and defence reactions. LOX represents the starting enzyme of the octadecanoid pathway. The aim of the work was to purify LOX from California poppy (Eschscholtzia [...] Read more.

Background: Plant lipoxygenases (LOXs, EC 1.13.11.12) are involved in lipid degradation, regulation of growth and development, senescence, and defence reactions. LOX represents the starting enzyme of the octadecanoid pathway. The aim of the work was to purify LOX from California poppy (Eschscholtzia californica Cham.), to determine its biochemical properties and to identify and quantify the products of LOX reaction with unsaturated fatty acids. Methods: LOX from California poppy seedlings was purified by hydrophobic chromatography (Phenyl-Sepharose CL-4B) and by ion-exchange chromatography (Q-Sepharose). The isolated LOX was incubated with linoleic acid used as a substrate. The HPLC experiments were performed with the Agilent Technologies 1050 series HPLC system. For the preparative separation of a mixture of hydroxy fatty acids from the sample matrix, the RP-HPLC method was used (column 120-5 Nucleosil C18). Then, the NP-HPLC analysis (separation, identification, and determination) of hydroxy fatty acid isomers was carried out on a Zorbax Rx-SIL column. Results: The purified LOX indicates the presence of a nontraditional plant enzyme with dual positional specificity (a ratio of 9- and 13-hydroperoxide products 1:1), a relative molecular mass of 85 kDa, a pH optimum of 6.5, an increasing activity stimulation by CaCl₂ till 2 mM, and a high substrate reactivity to linoleic acid with kinetic values of K_M 2.6 mM and V_max 3.14 μM/min/mg. Conclusions: For the first time, the LOX from California poppy seedlings was partially purified and the biochemical properties of the enzyme were analyzed. A dual positional specificity of the LOX found from California poppy seedlings is in agreement with the results obtained for LOXs isolated from other Papaveraceaes. A 1:1 ratio of 9-/13-HODE is attractive for the simultaneous investigation of both biotic stress responses (indicated by the 9-HODE marker) and the biosynthesis of jasmonic acid and jasmonates (indicated by the 13-HODE marker). Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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14 pages, 4388 KiB

Open AccessArticle

9,10-Dihydrophenanthrene with Two Spiro(dibenzocycloheptatriene) Units: A Highly Strained Caged Hydrocarbon Exhibiting Reversible Electrochromic Behavior

by Yusuke Ishigaki^*

, Yuki Hayashi, Kazuma Sugawara, Takuya Shimajiri, Wataru Nojo, Ryo Katoono and Takanori Suzuki^*

Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan

Molecules 2017, 22(11), 1900; https://doi.org/10.3390/molecules22111900 - 4 Nov 2017

Cited by 16 | Viewed by 7080

Abstract

The title dispiro hydrocarbon 1 was designed as a new electrochromic material. This multiply clamped hexaphenylethane-type electron donor was prepared from 2,2’-diiodobiphenyl via biphenyl-2,2’-diylbis(dibenzotropylium) 2²⁺ salt. X-ray analysis of 1 revealed a highly strained structure as reflected by an elongated “ethane” bond [...] Read more.

The title dispiro hydrocarbon 1 was designed as a new electrochromic material. This multiply clamped hexaphenylethane-type electron donor was prepared from 2,2’-diiodobiphenyl via biphenyl-2,2’-diylbis(dibenzotropylium) 2²⁺ salt. X-ray analysis of 1 revealed a highly strained structure as reflected by an elongated “ethane” bond [bond length: 1.6665(17) Å] and nearly eclipsed conformation. The weakened bond was cleaved upon two-electron oxidation to regenerate the deeply colored dication 2²⁺. The reversible interconversion between 1 and 2²⁺ is accompanied not only by a drastic color change but also by C–C bond formation/cleavage. Thus, the voltammogram showed a pair of well-separated redox waves, which is characteristic of “dynamic redox (dyrex)” behavior. The tetrahydro derivative of 1 with two units of spiro(dibenzocycloheptadiene), which suffers from more severe steric congestion, was also prepared. The crystallographically determined bond length for the central C–C bond [1.705(4) Å] is greatest among the values reported for 9,9,10,10-tetraaryl-9,10-dihydrophenanthrene derivatives. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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29 pages, 6934 KiB

Open AccessReview

First-Row Late Transition Metals for Catalytic Alkene Hydrofunctionalisation: Recent Advances in C-N, C-O and C-P Bond Formation

by Sophie Bezzenine-Lafollée¹, Richard Gil¹, Damien Prim²

and Jérôme Hannedouche^1,3,*

¹ Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), UMR 8182, University of Paris-Sud, F-91405 Orsay, France

² Institut Lavoisier de Versailles (ILV), UMR 8180, Université Versailles Saint-Quentin, F-78035 Versailles, France

³ Centre National de la Recherche Scientifique (CNRS), UMR8000, Laboratoire de Chimie Physique, F-91405 Orsay, France

Molecules 2017, 22(11), 1901; https://doi.org/10.3390/molecules22111901 - 4 Nov 2017

Cited by 72 | Viewed by 10890

Abstract

This review provides an outline of the most noteworthy achievements in the area of C-N, C-O and C-P bond formation by hydroamination, hydroalkoxylation, hydrophosphination, hydrophosphonylation or hydrophosphinylation reaction on unactivated alkenes (including 1,2- and 1,3-dienes) promoted by first-row late transition metal catalytic systems [...] Read more.

This review provides an outline of the most noteworthy achievements in the area of C-N, C-O and C-P bond formation by hydroamination, hydroalkoxylation, hydrophosphination, hydrophosphonylation or hydrophosphinylation reaction on unactivated alkenes (including 1,2- and 1,3-dienes) promoted by first-row late transition metal catalytic systems based on manganese, iron, cobalt, nickel, copper and zinc. The relevant literature from 2009 until mid-2017 has been covered. Full article

(This article belongs to the Special Issue Hydrofunctionalization and Hydrogenation with Earth Abundant Metals)

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30 pages, 11469 KiB

Open AccessReview

Lanthanide Photoluminescence in Heterometallic Polycyanidometallate-Based Coordination Networks

by Szymon Chorazy^*

, Maciej Wyczesany and Barbara Sieklucka

Faculty of Chemistry, Jagiellonian University in Kraków, Gronostajowa 2, 30-387 Kraków, Poland

Molecules 2017, 22(11), 1902; https://doi.org/10.3390/molecules22111902 - 4 Nov 2017

Cited by 61 | Viewed by 7253

Abstract

Solid-state functional luminescent materials arouse an enormous scientific interest due to their diverse applications in lighting, display devices, photonics, optical communication, low energy scintillation, optical storage, light conversion, or photovoltaics. Among all types of solid luminophors, the emissive coordination polymers, especially those based [...] Read more.

Solid-state functional luminescent materials arouse an enormous scientific interest due to their diverse applications in lighting, display devices, photonics, optical communication, low energy scintillation, optical storage, light conversion, or photovoltaics. Among all types of solid luminophors, the emissive coordination polymers, especially those based on luminescent trivalent lanthanide ions, exhibit a particularly large scope of light-emitting functionalities, fruitfully investigated in the aspects of chemical sensing, display devices, and bioimaging. Here, we present the complete overview of one of the promising families of photoluminescent coordination compounds, that are heterometallic d–f cyanido-bridged networks composed of lanthanide(3+) ions connected through cyanide bridges with polycyanidometallates of d-block metal ions. We are showing that the combination of cationic lanthanide complexes of selected inorganic and organic ligands with anionic homoligand [M(CN)x]ⁿ⁻ (x = 2, 4, 6 and 8) or heteroligand [M(L)(CN)4]²⁻ (L = bidentate organic ligand, M = transition metal ions) anions is the efficient route towards the emissive coordination networks revealing important optical properties, including 4f-metal-centred visible and near-infrared emission sensitized through metal-to-metal and/or ligand-to-metal energy transfer processes, and multi-coloured photoluminescence switchable by external stimuli such as excitation wavelength, temperature, or pressure. Full article

(This article belongs to the Special Issue Lanthanide Luminescence: Fundamental Research and Applications)

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12 pages, 552 KiB

Open AccessArticle

Effects of Chitooligosaccharide Coating Combined with Selected Ionic Polymers on the Stimulation of Ornithogalum saundersiae Growth

by Piotr Salachna^1,*

, Monika Grzeszczuk¹ and Marcin Soból²

¹ Department of Horticulture, West Pomeranian University of Technology, 3 Papieża Pawła VI Str., 71-434 Szczecin, Poland

² Center of Bioimmobilisation and Innovative Packaging Materials, West Pomeranian University of Technology, 35 Janickiego Str., 71-270 Szczecin, Poland

Molecules 2017, 22(11), 1903; https://doi.org/10.3390/molecules22111903 - 4 Nov 2017

Cited by 18 | Viewed by 5540

Abstract

Recently, agricultural and horticultural sectors have shown an increased interest in the use of biopolymers and their derivatives as growth biostimulators. So far, coating is a little known method of applying the biostimulators. Our three-year study investigated coating the bulbs of Ornithogalum saundersiae [...] Read more.

Recently, agricultural and horticultural sectors have shown an increased interest in the use of biopolymers and their derivatives as growth biostimulators. So far, coating is a little known method of applying the biostimulators. Our three-year study investigated coating the bulbs of Ornithogalum saundersiae with chitooligosaccharide (COS), sodium alginate, carrageenan, gellan gum and xanthan gum. The coating method was based on the formation of polyelectrolyte complexes. The COS with 48,000 g mol⁻¹ molecular weight was contained by means of controlled free-radical degradation. Biopolymer coatings stimulated plant growth and flowering, total chlorophyll content, total polyphenol content and the levels of nitrogen, phosphorus, potassium and boron. The plants grown from the bulbs coated with COS + gellan gum exhibited the most vigorous growth, were first to flower, showed the highest antioxidant activity (DPPH), and the greatest content of pigments, polyphenols, l-ascorbic acid, potassium, phosphorus, zinc and manganese. These results suggest COS formulated with gellan gum shows promise as a potential biostimulator of plant growth. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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13 pages, 2388 KiB

Open AccessArticle

The Oligomeric Form of the Escherichia coli Dps Protein Depends on the Availability of Iron Ions

by Sergey Antipov^1,2,3

, Sergey Turishchev³, Yuriy Purtov², Uliana Shvyreva², Alexander Sinelnikov³, Yuriy Semov³, Elena Preobrazhenskaya², Andrey Berezhnoy³, Natalia Shusharina¹, Natalia Novolokina³, Viktor Vakhtel³, Valeriy Artyukhov³ and Olga Ozoline^2,4,5,*

¹ School of Life Sciences, Immanuel Kant Baltic Federal University, 236016 Kaliningrad, Russia

² Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia

³ Department of Biophysics and Biotechnology, Voronezh State University, 394018 Voronezh, Russia

⁴ Department of Cell Biology, Pushchino State Institute of Natural Sciences, 142290 Pushchino, Russia

⁵ Department of Structural and Functional genomics, Pushchino Scientific Center, 142290 Pushchino, Russia

Molecules 2017, 22(11), 1904; https://doi.org/10.3390/molecules22111904 - 5 Nov 2017

Cited by 18 | Viewed by 5710

Abstract

The Dps protein of Escherichia coli, which combines ferroxidase activity and the ability to bind DNA, is effectively used by bacteria to protect their genomes from damage. Both activities depend on the integrity of this multi-subunit protein, which has an inner cavity [...] Read more.

The Dps protein of Escherichia coli, which combines ferroxidase activity and the ability to bind DNA, is effectively used by bacteria to protect their genomes from damage. Both activities depend on the integrity of this multi-subunit protein, which has an inner cavity for iron oxides; however, the diversity of its oligomeric forms has only been studied fragmentarily. Here, we show that iron ions stabilize the dodecameric form of Dps. This was found by electrophoretic fractionation and size exclusion chromatography, which revealed several oligomers in highly purified protein samples and demonstrated their conversion to dodecamers in the presence of 1 mM Mohr’s salt. The transmission electron microscopy data contradicted the assumption that the stabilizing effect is given by the optimal core size formed in the inner cavity of Dps. The charge state of iron ions was evaluated using Mössbauer spectroscopy, which showed the presence of Fe₃O₄, rather than the expected Fe₂O₃, in the sample. Assuming that Fe²⁺ can form additional inter-subunit contacts, we modeled the interaction of FeO and Fe₂O₃ with Dps, but the binding sites with putative functionality were predicted only for Fe₂O₃. The question of how the dodecameric form can be stabilized by ferric oxides is discussed. Full article

(This article belongs to the Special Issue Metallopeptides)

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8 pages, 1440 KiB

Open AccessArticle

Amaranth Protein Hydrolysates Efficiently Reduce Systolic Blood Pressure in Spontaneously Hypertensive Rats

by Giovanni Ramírez-Torres^1,2, Noé Ontiveros^3,*, Verónica Lopez-Teros¹

, Jesús Aurelio Ibarra-Diarte³, Cuauhtémoc Reyes-Moreno⁴, Edith Oliva Cuevas-Rodríguez⁴ and Francisco Cabrera-Chávez^2,3,*

¹ Nutritional Sciences, Department of Chemical and Biological Sciences, University of Sonora, Hermosillo, Sonora 83000, Mexico

² Faculty of Physical Education and Sport, University of Sinaloa, Culiacán, Sinaloa 80019, Mexico

³ Nutrition Sciences Academic Unit, University of Sinaloa, Culiacán, Sinaloa 80019, Mexico

⁴ Faculty of Chemical and Biological Sciences, University of Sinaloa, Culiacán, Sinaloa 80199, Mexico

Molecules 2017, 22(11), 1905; https://doi.org/10.3390/molecules22111905 - 9 Nov 2017

Cited by 30 | Viewed by 5315

Abstract

Alcalase is the enzyme of choice to release antihypertensive peptides from amaranth proteins, but the hydrolysis conditions have not been optimized yet. Furthermore, in vivo assays are needed to confirm such a hypotensive effect. Our aim was to optimize the hydrolysis of amaranth [...] Read more.

Alcalase is the enzyme of choice to release antihypertensive peptides from amaranth proteins, but the hydrolysis conditions have not been optimized yet. Furthermore, in vivo assays are needed to confirm such a hypotensive effect. Our aim was to optimize the hydrolysis of amaranth protein with alcalase and to test in vivo the hypotensive effect of the hydrolysates. A response surface analysis was carried out to optimize the hydrolysis reaction. The response variable was the Angiotensin Converting Enzyme (ACE-I) inhibition. The hydrolysis degree was determined (free alpha-amino groups measurement). The optimized hydrolysate bioavailability was assessed in the sera of mice and the hypotensive effect was assessed in spontaneously hypertensive rats. Control groups were administered captopril or water. The optimized hydrolysis conditions were: pH = 7.01, temperature = 52 °C, enzyme concentration 0.04 mU/mg, and time = 6.16 h. The optimized hydrolysate showed a 93.5% of ACE-I inhibition and a hydrolysis degree of 74.77%. After supplementation, the hydrolysate was bioavailable in mice from 5 to 60 min, and the hypotensive effect started at 4 h in spontaneously hypertensive rats (p < 0.05 vs. water group). This effect was similar to the captopril hypotensive effect for the next 3 h (p > 0.05). The use of amaranth-optimized hydrolysates as hypotensive supplements or ingredient for functional foods seems feasible. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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15 pages, 11959 KiB

Open AccessArticle

Biophysical and In Silico Studies of the Interaction between the Anti-Viral Agents Acyclovir and Penciclovir, and Human Serum Albumin

by Ali S. Abdelhameed^1,*

, Ahmed H. Bakheit^1,2, Fahad M. Almutairi³, Haitham AlRabiah¹ and Adnan A. Kadi¹

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

² Department of Chemistry, Faculty of Science and Technology, El-Neelain University, P.O. Box 12702, Khartoum 11121, Sudan

³ Department of Biochemistry, Faculty of Science, University of Tabuk, P.O. Box 741, Tabuk 71491, Saudi Arabia

Molecules 2017, 22(11), 1906; https://doi.org/10.3390/molecules22111906 - 5 Nov 2017

Cited by 38 | Viewed by 5095

Abstract

Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced [...] Read more.

Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced spectroscopic and in-silico methods. The interactions between ACV/PNV and HSA at the three investigated temperatures revealed a static type of binding. Extraction of the thermodynamic parameters of the ACV-HSA and PNV-HSA systems from the measured spectrofluorimetric data demonstrated spontaneous interactions with an enthalpy change (∆H⁰) of −1.79 ± 0.29 and −4.47 ± 0.51 kJ·mol⁻¹ for ACV and PNV, respectively. The entropy change (∆S⁰) of 79.40 ± 0.95 and 69.95 ± 1.69 J·mol⁻¹·K⁻¹ for ACV and PNV, respectively, hence supported a potential contribution of electrostatic binding forces to the ACV-HSA and PNV-HSA systems. Putative binding of ACV/PNV to HSA, using previously reported site markers, showed that ACV/PNV were bound to HSA within subdomains IIA and IIIA (Sudlow sites I and II). Further confirmation was obtained through molecular docking studies of ACV-HSA and PNV-HSA binding, which confirmed the binding site of ACV/PNV with the most stable configurations of ACV/PNV within the HSA. These ACV/PNV conformers were shown to have free energies of −25.61 and −22.01 kJ·mol⁻¹ for ACV within the HSA sites I and II and −22.97 and −26.53 kJ·mol⁻¹ for PNV in HSA sites I and II, with hydrogen bonding and electrostatic forces being the main binding forces in such conformers. Full article

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13 pages, 2656 KiB

Open AccessArticle

Enhanced Agronomic Traits and Medicinal Constituents of Autotetraploids in Anoectochilus formosanus Hayata, a Top-Grade Medicinal Orchid

by Hsiao-Hang Chung¹, Shu-Kai Shi², Bin Huang³ and Jen-Tsung Chen^2,*

¹ Department of Horticulture, National Ilan University, Yilan City 260, Taiwan

² Department of Life Sciences, National University of Kaohsiung, Kaohsiung 811, Taiwan

³ Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Molecules 2017, 22(11), 1907; https://doi.org/10.3390/molecules22111907 - 7 Nov 2017

Cited by 40 | Viewed by 7993

Abstract

This study developed an efficient and reliable system for inducing polyploidy in Anoectochilus formosanus Hayata, a top-grade medicinal orchid. The resulting tetraploid gave a significant enhancement on various agronomic traits, including dry weight, fresh weight, shoot length, root length, leaf width, the size [...] Read more.

This study developed an efficient and reliable system for inducing polyploidy in Anoectochilus formosanus Hayata, a top-grade medicinal orchid. The resulting tetraploid gave a significant enhancement on various agronomic traits, including dry weight, fresh weight, shoot length, root length, leaf width, the size of stoma, and number of chloroplasts per stoma. A reduction of the ratio of length to width was observed in stomata and leaves of the tetraploid, and consequently, an alteration of organ shape was found. The major bioactive compounds, total flavonoid and gastrodin, were determined by the aluminum chloride colorimetric method and ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), respectively. The tetraploid produced significantly higher contents of total flavonoid and gastrodin in the leaf, the stem, and the whole plant when compared with the diploid. The resulting tetraploids in this study are proposed to be suitable raw materials in the pharmaceutical industry for enhancing productivity and reducing cost. Full article

(This article belongs to the Collection Herbal Medicine Research)

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15 pages, 3902 KiB

Open AccessArticle

Chitin and Cellulose Processing in Low-Temperature Electron Beam Plasma

by Tatiana Vasilieva^1,*, Dmitry Chuhchin², Sergey Lopatin³, Valery Varlamov³, Andrey Sigarev¹ and Michael Vasiliev¹

¹ Moscow Institute of Physics and Technology, Institutsky per., 9, Dolgoprudny, 141700 Moscow, Russia

² Core Facility Center “Arktika”, Northern (Arctic) Federal University, Severnaya Dvina Emb., 17, 163002 Arkhangelsk, Russia

³ Federal State Institution, Federal Research Centre, Fundamentals of Biotechnology of RAS, Institute of Bioengineering, 60 let Oktjabrja pr-t, 7/1, 117312 Moscow, Russia

Molecules 2017, 22(11), 1908; https://doi.org/10.3390/molecules22111908 - 6 Nov 2017

Cited by 20 | Viewed by 6230

Abstract

Polysaccharide processing by means of low-temperature Electron Beam Plasma (EBP) is a promising alternative to the time-consuming and environmentally hazardous chemical hydrolysis in oligosaccharide production. The present paper considers mechanisms of the EBP-stimulated destruction of crab shell chitin, cellulose sulfate, and microcrystalline cellulose, [...] Read more.

Polysaccharide processing by means of low-temperature Electron Beam Plasma (EBP) is a promising alternative to the time-consuming and environmentally hazardous chemical hydrolysis in oligosaccharide production. The present paper considers mechanisms of the EBP-stimulated destruction of crab shell chitin, cellulose sulfate, and microcrystalline cellulose, as well as characterization of the produced oligosaccharides. The polysaccharide powders were treated in oxygen EBP for 1–20 min at 40 °C in a mixing reactor placed in the zone of the EBP generation. The chemical structure and molecular mass of the oligosaccharides were analyzed by size exclusion and the reversed phase chromatography, FTIR-spectroscopy, XRD-, and NMR-techniques. The EBP action on original polysaccharides reduces their crystallinity index and polymerization degree. Water-soluble products with lower molecular weight chitooligosaccharides (weight-average molecular mass, M_w = 1000–2000 Da and polydispersity index 2.2) and cellulose oligosaccharides with polymerization degrees 3–10 were obtained. The ¹H-NMR analysis revealed 25–40% deacetylation of the EBP-treated chitin and FTIR-spectroscopy detected an increase of carbonyl- and carboxyl-groups in the oligosaccharides produced. Possible reactions of β-1,4-glycosidic bonds’ destruction due to active oxygen species and high-energy electrons are given. Full article

(This article belongs to the Special Issue Advances in Natural Polysaccharides Research)

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9 pages, 232 KiB

Open AccessCommunication

Headspace Solid-Phase Microextraction and Ultrasonic Extraction with the Solvent Sequences in Chemical Profiling of Allium ursinum L. Honey

by Igor Jerković^1,*

and Piotr M. Kuś²

¹ Department of Organic Chemistry, Faculty of Chemistry and Technology, University of Split, Rudera Boskovica 35, 21000 Split, Croatia

² Department of Pharmacognosy, Wroclaw Medical University, ul. Borowska 211a, 50-556 Wroclaw, Poland

Molecules 2017, 22(11), 1909; https://doi.org/10.3390/molecules22111909 - 6 Nov 2017

Cited by 5 | Viewed by 4273

Abstract

A volatile profile of ramson (wild garlic, Allium ursinum L.) honey was investigated by headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE) followed by gas chromatography and mass spectrometry (GC-FID/GC-MS) analyses. The headspace was dominated by linalool derivatives: cis- and trans [...] Read more.

A volatile profile of ramson (wild garlic, Allium ursinum L.) honey was investigated by headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE) followed by gas chromatography and mass spectrometry (GC-FID/GC-MS) analyses. The headspace was dominated by linalool derivatives: cis- and trans-linalool oxides (25.3%; 9.2%), hotrienol (12.7%), and linalool (5.8%). Besides direct extraction with dichloromethane and pentane/diethyl ether mixture (1:2, v/v), two solvent sequences (I: pentane → diethyl ether; II: pentane → pentane/diethyl ether (1:2, v/v) → dichloromethane) were applied. Striking differences were noted among the obtained chemical profiles. The extracts with diethyl ether contained hydroquinone (25.8–36.8%) and 4-hydroxybenzoic acid (11.6–16.6%) as the major compounds, while (E)-4-(r-1′,t-2′,c-4′-trihydroxy-2′,6′,6′-trimethylcyclohexyl)but-3-en-2-one predominated in dichloromethane extracts (18.3–49.1%). Therefore, combination of different solvents was crucial for the comprehensive investigation of volatile organic compounds in this honey type. This particular magastigmane was previously reported only in thymus honey and hydroquinone in vipers bugloss honey, while a combination of the mentioned predominant compounds is unique for A. ursinum honey. Full article

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

14 pages, 3930 KiB

Open AccessArticle

Interaction of α- and β-zearalenols with β-cyclodextrins

by Miklós Poór^1,2,*, Afshin Zand¹

, Lajos Szente³, Beáta Lemli^2,4 and Sándor Kunsági-Máté^2,4

¹ Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary

² János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary

³ CycloLab Cyclodextrin Research & Development Laboratory, Ltd., Illatos út 7, H-1097 Budapest, Hungary

⁴ Department of General and Physical Chemistry, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary

Molecules 2017, 22(11), 1910; https://doi.org/10.3390/molecules22111910 - 6 Nov 2017

Cited by 18 | Viewed by 4144

Abstract

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. ZEN primarily contaminates different cereals, and exerts a strong xenoestrogenic effect in animals and humans. ZEN is a fluorescent mycotoxin, although molecular interactions and microenvironmental changes significantly modify its spectral properties. During biotransformation, ZEN [...] Read more.

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. ZEN primarily contaminates different cereals, and exerts a strong xenoestrogenic effect in animals and humans. ZEN is a fluorescent mycotoxin, although molecular interactions and microenvironmental changes significantly modify its spectral properties. During biotransformation, ZEN is converted into α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL), the toxic metabolites of ZEN, which mimick the effect of estrogen. Cyclodextrins (CDs) are host molecules, and have been studied extensively; they can form stable complexes with several mycotoxins, including ZEN. However, information is limited regarding the interactions of CDs with ZOLs. Therefore, we studied the interactions of α- and β-ZOLs with native and six chemically modified β-CDs by fluorescence spectroscopy. Fluorescence enhancement during complex formation, as well as binding constants, were determined. To understand ZOL-CD interactions better, molecular modeling studies were also carried out. Both mycotoxin derivatives formed the most stable complexes with methylated and sulfobutylated CD-derivatives; however, the CD complexes of α-ZOL were significantly stronger than those of β-ZOL. The data presented here indicate which of the chemically modified β-CDs appear more suitable as fluorescence enhancers or as potential mycotoxin binders. Full article

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12 pages, 1110 KiB

Open AccessArticle

Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis

by Lukáš Slovák^1,*, Karol Švík¹, Danica Mihalová¹, Jaroslav Tóth²

, Szilvia Czigle², Ľudmila Pašková²

, František Bilka² and Katarína Bauerová^1,2,*

¹ Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, Slovakia

² Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia

Molecules 2017, 22(11), 1911; https://doi.org/10.3390/molecules22111911 - 6 Nov 2017

Cited by 15 | Viewed by 4603

Abstract

Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA [...] Read more.

Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or in combination in adjuvant arthritis. The disease was induced to Lewis male rats by intradermal injection, which contains a suspension of heat-inactivated Mycobacterium butyricum in incomplete Freund’s adjuvant. The experiment of 28 days included: healthy animals, arthritic animals, arthritic animals with administration of FRA at the oral daily dose of 15 mg/kg, arthritic animals with administration of MTX at the oral dose of 0.3 mg/kg twice a week, and arthritic animals administered with FRA and MTX. FRA in monotherapy decreased significantly only the level of interleukin-1β (IL-1β) and matrix metalloproteinase-9 in plasma. Combination of FRA and low-dose MTX was more effective than MTX alone when comparing body weight, hind paw volume, arthritic score, plasmatic levels of IL-1β, activity of γ-glutamyl transferase, and relative mRNA expression of IL-1β in the spleen. Therefore, the combination treatment was the most effective. The obtained results are interesting for future possible innovative therapy of patients with RA. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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9 pages, 4250 KiB

Open AccessArticle

Mechanistic Study of Copper-Catalyzed C-H Hydroxylation/C-S Coupling by ESI-HR MS and DFT Calculations

by Runsheng Xu^*, Rongrong Cai, Sixian Zhou, Zhuoda Zhou, Beibei Li and Dihui Xu

Department of Biology and Environment, Jiyang College of Zhejiang A&F University, Shaoxing 311800, China

Molecules 2017, 22(11), 1912; https://doi.org/10.3390/molecules22111912 - 6 Nov 2017

Cited by 1 | Viewed by 5239

Abstract

The reaction mechanism of Cu-catalyzed C-H hydroxylation/C-S coupling was studied using electrospray ionization high resolution mass spectrometry (ESI-HR MS) and density functional theory calculations (DFT). Notably, a series of Cu^I and Cu^III complexes were observed as key intermediates and identified using [...] Read more.

The reaction mechanism of Cu-catalyzed C-H hydroxylation/C-S coupling was studied using electrospray ionization high resolution mass spectrometry (ESI-HR MS) and density functional theory calculations (DFT). Notably, a series of Cu^I and Cu^III complexes were observed as key intermediates and identified using ESI-HR MS. Furthermore, a catalyst cycle involving proton abstraction/oxidative addition/reductive elimination was proposed. This study is important and valuable with respect to C-H functionalization. Full article

(This article belongs to the Special Issue The Molecular Electron Density Theory: A Modern View of Molecular Reactivity in Organic Chemistry)

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11 pages, 2106 KiB

Open AccessArticle

Antibacterial Activity of Polyphenols: Structure-Activity Relationship and Influence of Hyperglycemic Condition

by Yixi Xie^1,2

, Jing Chen¹, Aiping Xiao¹ and Liangliang Liu^1,*

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

² College of Chemistry, Xiangtan University, Xiangtan 411105, China

Molecules 2017, 22(11), 1913; https://doi.org/10.3390/molecules22111913 - 6 Nov 2017

Cited by 95 | Viewed by 6250

Abstract

Polyphenols are plant-derived natural products with well-documented health benefits to human beings, such as antibacterial activities. However, the antibacterial activities of polyphenols under hyperglycemic conditions have been rarely studied, which could be relevant to their antibacterial efficacy in disease conditions, such as in [...] Read more.

Polyphenols are plant-derived natural products with well-documented health benefits to human beings, such as antibacterial activities. However, the antibacterial activities of polyphenols under hyperglycemic conditions have been rarely studied, which could be relevant to their antibacterial efficacy in disease conditions, such as in diabetic patients. Herein, the antibacterial activities of 38 polyphenols under mimicked hyperglycemic conditions were evaluated. The structure-antibacterial activity relationships of polyphenols were also tested and analyzed. The presence of glucose apparently promoted the growth of the bacterial strains tested in this study. The OD600 values of tested bacteria strains increased from 1.09-fold to 1.49-fold by adding 800 mg/dL glucose. The polyphenols showed structurally dependent antibacterial activities, which were significantly impaired under the hyperglycemic conditions. The results from this study indicated that high blood glucose might promote bacterial infection, and the hyperglycemic conditions resulting from diabetes were likely to suppress the antibacterial benefits of polyphenols. Full article

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10 pages, 2042 KiB

Open AccessArticle

Evaluating the Potential Value of Natural Product Cuminic Acid against Plant Pathogenic Fungi in Cucumber

by Yong Wang^†, Jie Zhang^†, Yang Sun, Juntao Feng and Xing Zhang^*

¹ Research and Development Center of Biorational Pesticides, Northwest A & F University, Yangling 712100, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1914; https://doi.org/10.3390/molecules22111914 - 6 Nov 2017

Cited by 9 | Viewed by 4983

Abstract

Fusarium wilt and anthracnose are two major diseases which limit the yield and quality of cucumber worldwide. Cuminic acid was extracted from the seed of Cuminum cyminum L. The mean EC₅₀ values of cuminic acid for inhibiting mycelial growth and zoospore germination [...] Read more.

Fusarium wilt and anthracnose are two major diseases which limit the yield and quality of cucumber worldwide. Cuminic acid was extracted from the seed of Cuminum cyminum L. The mean EC₅₀ values of cuminic acid for inhibiting mycelial growth and zoospore germination of five Fusarium oxysporum f. sp. cucumerinum strains were 25.66 ± 3.02 μg/mL and 15.99 ± 2.19 μg/mL, and of four Colletotrichum lagenarium (Pass.) Ellis and Halsted strains were 29.53 ± 3.18 μg/mL and 18.41 ± 2.78 μg/mL, respectively. In greenhouse experiments, cuminic acid at 2000 μg/mL exhibited 70.77% protective and 62.63% curative efficacies against F. oxysporum, and 65.43% protective and 55.46% curative efficacies against C. lagenarium. Moreover, the translocation behavior of cuminic acid, determined by high performance liquid chromatography (HPLC), showed that it could be readily absorbed and transported upward and downward in cucumber. Importantly, superoxide dismutase (SOD) and pyphenol oxidase (PPO) activities of cucumber leaves treated with cuminic acid increased significantly. All results indicated that cuminic acid showed antifungal activity, and could be used as a botanical fungicide in disease management. This study encourages further investigation on the mechanism of action of cuminic acid and the development of alternative antifungal drugs. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 951 KiB

Open AccessReview

Oleanolic Acid and Its Derivatives: Biological Activities and Therapeutic Potential in Chronic Diseases

by Taiwo Betty Ayeleso

, Mashudu Given Matumba and Emmanuel Mukwevho^*

Department of Biochemistry, North West University, Private Bag X2046, Mmabatho 2735, South Africa

Molecules 2017, 22(11), 1915; https://doi.org/10.3390/molecules22111915 - 13 Nov 2017

Cited by 251 | Viewed by 14344

Abstract

The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA) in the [...] Read more.

The increasing demand for natural products as an alternative therapy for chronic diseases has encouraged research into the pharmacological importance of bioactive compounds from plants. Recently, there has been a surge of interest in the therapeutic potential of oleanolic acid (OA) in the prevention and management of chronic diseases. Oleanolic acid is a pentacyclic triterpenoid widely found in plants, including fruits and vegetables with different techniques and chromatography platforms being employed in its extraction and isolation. Several studies have demonstrated the potential therapeutic effects of OA on different diseases and their symptoms. Furthermore, oleanolic acid also serves as a framework for the development of novel semi-synthetic triterpenoids that could prove vital in finding therapeutic modalities for various ailments. There are recent advances in the design and synthesis of chemical derivatives of OA to enhance its solubility, bioavailability and potency. Some of these derivatives have also been therapeutic candidates in a number of clinical trials. This review consolidates and expands on recent reports on the biological effects of oleanolic acid from different plant sources and its synthetic derivatives as well as their mechanisms of action in in vitro and in vivo study models. This review suggests that oleanolic acid and its derivatives are important candidates in the search for alternative therapy in the treatment and management of chronic diseases. Full article

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

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8 pages, 5077 KiB

Open AccessCommunication

Non-Covalent Loading of Anti-Cancer Doxorubicin by Modularizable Peptide Self-Assemblies for a Nanoscale Drug Carrier

by Kin-ya Tomizaki^1,2,*, Kohei Kishioka¹, Shunsuke Kataoka¹, Makoto Miyatani¹, Takuya Ikeda¹, Mami Komada³, Takahito Imai¹ and Kenji Usui^3,*

¹ Department of Materials Chemistry, Ryukoku University, 1-5 Yokotani, Seta-Oe, Otsu 520-2194, Japan

² Innovative Materials and Processing Research Center, Ryukoku University, 1-5 Yokotani, Seta-Oe, Otsu 520-2194, Japan

³ Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minami, Chuo, Kobe 650-0047, Japan

Molecules 2017, 22(11), 1916; https://doi.org/10.3390/molecules22111916 - 6 Nov 2017

Cited by 9 | Viewed by 5484

Abstract

We prepared nanoscale, modularizable, self-assembled peptide nanoarchitectures with diameters less of than 20 nm by combining β-sheet-forming peptides tethering a cell-penetrating peptide or a nuclear localization signal sequence. We also found that doxorubicin (Dox), an anti-cancer drug, was non-covalently accommodated by the assemblies [...] Read more.

We prepared nanoscale, modularizable, self-assembled peptide nanoarchitectures with diameters less of than 20 nm by combining β-sheet-forming peptides tethering a cell-penetrating peptide or a nuclear localization signal sequence. We also found that doxorubicin (Dox), an anti-cancer drug, was non-covalently accommodated by the assemblies at a ratio of one Dox molecule per ten peptides. The Dox-loaded peptide assemblies facilitated cellular uptake and subsequent nuclear localization in HeLa cells, and induced cell death even at low Dox concentrations. This peptide nanocarrier motif is a promising platform for a biocompatible drug delivery system by altering the targeting head groups of the carrier peptides. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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10 pages, 2950 KiB

Open AccessArticle

Yarrowia lipolytica Extracellular Lipase Lip2 as Biocatalyst for the Ring-Opening Polymerization of ε-Caprolactone

by Karla A. Barrera-Rivera^* and Antonio Martínez-Richa^*

Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Colonia Noria Alta, Guanajuato, Guanajuato 36050, Mexico

Molecules 2017, 22(11), 1917; https://doi.org/10.3390/molecules22111917 - 7 Nov 2017

Cited by 9 | Viewed by 5286

Abstract

Yarrowia lipolytica (YL) is a “non-conventional” yeast that is capable of producing important metabolites. One of the most important products that is secreted by this microorganism is lipase, a ubiquitous enzyme that has considerable industrial potential and can be used as a biocatalyst [...] Read more.

Yarrowia lipolytica (YL) is a “non-conventional” yeast that is capable of producing important metabolites. One of the most important products that is secreted by this microorganism is lipase, a ubiquitous enzyme that has considerable industrial potential and can be used as a biocatalyst in the pharmaceutical, food, and environmental industries. In this work, Yarrowia lipolytica lipase (YLL) was immobilized on Lewatit and Amberlite beads and is used in the enzymatic ring-opening polymerization (ROP) of cyclic esters in the presence of different organic solvents. YLL immobilized on Amberlite XAD7HP had the higher protein adsorption (96%) and a lipolytic activity of 35 U/g. Lewatit VPOC K2629 has the higher lipolytic activity (805 U/g) and 92% of protein adsorption. The highest molecular weight (Mn 10,685 Da) was achieved at 90 °C using YLL that was immobilized on Lewatit 1026 with decane as solvent after 60 h and 100% of monomer conversion. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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11 pages, 8819 KiB

Open AccessArticle

Effects of Polysaccharides from Platycodon grandiflorum on Immunity-Enhancing Activity In Vitro

by Xiaona Zhao^1,†, Yuge Wang^2,†, Peng Yan¹, Guodong Cheng¹, Cheng Wang¹, Na Geng¹, Xuepeng Wang^3,* and Jianzhu Liu^1,2,*

¹ College of Animal Medicine and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China

² Research Center for Animal Disease Control Engineering Shandong Province, Shandong Agricultural University, Tai’an 271018, China

³ Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai’an 271018, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1918; https://doi.org/10.3390/molecules22111918 - 7 Nov 2017

Cited by 52 | Viewed by 6331

Abstract

The study is aimed at investigating the immunoenhancement activity of polysaccharides from Platycodon grandiflorum polysaccharides (PGPSs) in vitro. In this study, some research on lymphocyte proliferation, cell cycle, and the levels of CD4⁺ and CD8⁺ T cells were performed. Four different [...] Read more.

The study is aimed at investigating the immunoenhancement activity of polysaccharides from Platycodon grandiflorum polysaccharides (PGPSs) in vitro. In this study, some research on lymphocyte proliferation, cell cycle, and the levels of CD4⁺ and CD8⁺ T cells were performed. Four different concentrations of PGPSs (PGPS_tc, PGPS_60c, PGPS_80c, and PGPS_tp) were harvested and added to peripheral blood T lymphocytes. We observed significant increases in T lymphocyte proliferation at PGPS_tc groups individually or synergistically with phytohemagglutinin (PHA) at most concentrations, and their lymphocyte proliferation rates were the highest. The active sites of PGPS_tc and PGPS_60c were subsequently chosen. Then, we utilized flow cytometry to determine lymphocyte cell cycle distribution and levels of CD4⁺ and CD8⁺ T cells. At most time points, PGPS_tc could facilitate lymphocyte cell cycle progression from the G0/G1 phase to the S and G2/M phases and, simultaneously, increase the levels of CD4⁺ and CD8⁺ T cells. These results indicate that PGPS_tc enhances the immune functions, suggesting that PGPS_tc could be a potential immunopotentiator for further in vivo and clinical trial experiments. Full article

(This article belongs to the Special Issue Polysaccharide-based Materials)

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11 pages, 1707 KiB

Open AccessArticle

Antimicrobial Abietane-Type Diterpenoids from Plectranthus punctatus

by Negera Abdissa^1,2,*, Marcel Frese¹ and Norbert Sewald^1,*

¹ Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, P.O. Box 100131, Bielefeld 33501, Germany

² Department of Chemistry, College of Natural Sciences, Jimma University, P.O. Box 378, Jimma 251, Ethiopia

Molecules 2017, 22(11), 1919; https://doi.org/10.3390/molecules22111919 - 7 Nov 2017

Cited by 30 | Viewed by 6387

Abstract

Four new para-benzoquinone containing abietane-type diterpenoids (1–4) along with thirteen known diterpenoids (5–17) were isolated from the roots of Plectranthus punctatus. The structures of the compounds were established by detailed spectroscopic analyses and [...] Read more.

Four new para-benzoquinone containing abietane-type diterpenoids (1–4) along with thirteen known diterpenoids (5–17) were isolated from the roots of Plectranthus punctatus. The structures of the compounds were established by detailed spectroscopic analyses and comparison with literature data. The compounds were tested for their antibacterial and cytotoxic activity and showed significant inhibitory activity against all bacterial strains used, with compounds 6, 8, 10, and 11 showing an inhibition zone for Staphylococcus warneri even greater than the reference drug, gentamycin. Full article

(This article belongs to the Collection Bioactive Compounds)

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20 pages, 7926 KiB

Open AccessArticle

Characteristics of Multifunctional, Eco-Friendly Lignin-Al₂O₃ Hybrid Fillers and Their Influence on the Properties of Composites for Abrasive Tools

by Łukasz Klapiszewski^1,*

, Artur Jamrozik^1,2, Beata Strzemiecka¹, Iwona Koltsov³

, Bartłomiej Borek⁴, Danuta Matykiewicz⁵, Adam Voelkel¹ and Teofil Jesionowski¹

¹ Institute of Chemical Technology and Engineering, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, PL-60965 Poznan, Poland

² Wielkopolska Centre of Advanced Technologies, Umultowska 89 C, PL-61614 Poznan, Poland

³ Polish Academy of Sciences, Institute of High Pressure Physics, Sokolowska 29/37, PL-01142 Warszawa, Poland

⁴ RHL-Service, Budziszynska 74, PL-60179 Poznan, Poland

⁵ Institute of Materials Technology, Faculty of Mechanical Engineering and Management, Poznan University of Technology, Piotrowo 3, PL-61138 Poznan, Poland

Molecules 2017, 22(11), 1920; https://doi.org/10.3390/molecules22111920 - 7 Nov 2017

Cited by 27 | Viewed by 5517

Abstract

The main aim of the present study was the preparation and comprehensive characterization of innovative additives to abrasive materials based on functional, pro-ecological lignin-alumina hybrid fillers. The behavior of lignin, alumina and lignin-Al₂O₃ hybrids in a resin matrix was explained [...] Read more.

The main aim of the present study was the preparation and comprehensive characterization of innovative additives to abrasive materials based on functional, pro-ecological lignin-alumina hybrid fillers. The behavior of lignin, alumina and lignin-Al₂O₃ hybrids in a resin matrix was explained on the basis of their surface and application properties determined by inverse gas chromatography, the degree of adhesion/cohesion between components, thermomechanical and rheological properties. On the basis of the presented results, a hypothetical mechanism of interactions between lignin and Al₂O₃ as well as between lignin-Al₂O₃ hybrids and phenolic resins was proposed. It was concluded that lignin compounds can provide new, promising properties for a phenolic binder combining the good properties of this biopolymer as a plasticizer and of alumina as a filler improving mechanical and thermal properties. The use of such materials may be relatively non-complicated and efficient way to improve the performance of bonded abrasive tools. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

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11 pages, 804 KiB

Open AccessArticle

Natural Deep Eutectic Solvents (NADES) to Enhance Berberine Absorption: An In Vivo Pharmacokinetic Study

by Stefania Sut¹, Marta Faggian², Valeria Baldan¹, Gabriele Poloniato¹, Ignazio Castagliuolo³, Iztok Grabnar⁴, Beatrice Perissutti⁵, Paola Brun³, Filippo Maggi⁶, Dario Voinovich⁵, Gregorio Peron¹

and Stefano Dall’Acqua^1,*

¹ Department of Pharmaceutical and Pharmacological Sciences University of Padova, via Marzolo 5, 35121 Padova, Italy

² Unir&d, Nutraceutical lab, via Tommaseo, 35100 Padova, Italy

³ Department of Molecular Medicine University of Padova, via Gabelli, 35121 Padova, Italy

⁴ Faculty of Pharmacy, University of Ljubljana, Askerceva Cesta 7, SI-1000 Ljubljana, Slovenia

⁵ Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy

⁶ School of Pharmacy, University of Camerino, Via Sant’Agostino 1, I-62032 Camerino, Italy

Molecules 2017, 22(11), 1921; https://doi.org/10.3390/molecules22111921 - 8 Nov 2017

Cited by 102 | Viewed by 10881

Abstract

In the present study results related to the in vivo administration of Natural Deep Eutectic Solvents (NADES)-solubilized berberine are reported for the first time. NADES are mixtures of small natural compounds having a melting point significantly lower than that of any individual component. [...] Read more.

In the present study results related to the in vivo administration of Natural Deep Eutectic Solvents (NADES)-solubilized berberine are reported for the first time. NADES are mixtures of small natural compounds having a melting point significantly lower than that of any individual component. Such solvents have gained much attention of the scientific community in the green chemistry area, being considered useful alternatives to common organic solvents. NADES can be used also as administration vehicles, and this can be attractive for nutraceutical products when eutectics are formed with food grade ingredients. In this work, different NADES were prepared using mainly food grade constituents and were tested as solvents for the alkaloid berberine. Three selected NADES/berberine solutions and an aqueous suspension were orally administered to mice with in dose of 50 mg/Kg. Blood levels of berberine were measured by a LC-MS/MS method. The pharmacokinetic analysis revealed a 2–20 fold increase in blood concentration of NADES/berberine with significant changes in pharmacokinetic profile. Natural Deep Eutectic Solvents may thus be considered attractive solubilizing agents and may also play a role in the increase of absorption of poorly bioavailable natural products such as berberine. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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13 pages, 7648 KiB

Open AccessArticle

Peptide Nucleic Acid Based Molecular Authentication for Identification of Four Medicinal Paeonia Species Using Melting Array Analysis of the Internal Transcribed Spacer 2 Region

by Wook Jin Kim, Sungyu Yang, Goya Choi and Byeong Cheol Moon^*

K-herb Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 305-811, Korea

Molecules 2017, 22(11), 1922; https://doi.org/10.3390/molecules22111922 - 7 Nov 2017

Cited by 8 | Viewed by 5771

Abstract

Accurate taxonomic identification of plant materials in herbal medicines is important for product quality control. The genus Paeonia (Saxifragales) is the source of the herbal preparations Paeoniae Radix (Paeoniae Radix Alba and Paeoniae Radix Rubra) and Moutan Radicis Cotex. However, confusion has arisen [...] Read more.

Accurate taxonomic identification of plant materials in herbal medicines is important for product quality control. The genus Paeonia (Saxifragales) is the source of the herbal preparations Paeoniae Radix (Paeoniae Radix Alba and Paeoniae Radix Rubra) and Moutan Radicis Cotex. However, confusion has arisen regarding their contents due to linguistic and taxonomic ambiguities, similar morphologies and different definitions of Paeoniae Radix in the Korean and Chinese national pharmacopoeias, leading to the distribution of adulterated products. To develop a method for identifying the four Paeonia species used in these medicines, three fluorescently-labeled peptide nucleic acid (PNA) probes were designed against ITS2 sequences containing single nucleotide polymorphisms (SNPs) and used in a real-time PCR melting curve assay. Each of the four Paeonia species was accurately identified using this analysis. The accuracy and analytical stability of the PNA melting curve assay was confirmed using commercially available samples of the four Paeonia species. This assay is a reliable genetic tool to distinguish between different Paeonia-derived herbal medicines and identify the botanical origins of Paeoniae Radix and Moutan Radicis Cortex. This technique may also contribute to quality control and standardization of herbal medicines by providing a reliable authentication tool and preventing the distribution of inauthentic adulterants. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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13 pages, 1350 KiB

Open AccessArticle

Design, Synthesis and Anticancer Evaluation of Fangchinoline Derivatives

by Yazhou Liu^1,2,†, Bin Xia^1,2,†, Junjie Lan^1,2, Shengcao Hu^1,2, Lan Huang^1,2, Chao Chen^1,2, Xueyi Zeng^1,2, Huayong Lou^1,2, Changhu Lin^1,* and Weidong Pan^1,2,*

¹ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, China

² The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 3491 Baijin Road, Guiyang 550014, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1923; https://doi.org/10.3390/molecules22111923 - 8 Nov 2017

Cited by 15 | Viewed by 4931

Abstract

Twenty fangchinoline derivatives were synthesized from the natural product fangchinoline, and their anticancer activities on human breast cancer MDA-MB-231 cell line, human prostate cancer PC3 cell line, human melanoma WM9 cell line and human leukaemia HEL and K562 cell lines were evaluated. The [...] Read more.

Twenty fangchinoline derivatives were synthesized from the natural product fangchinoline, and their anticancer activities on human breast cancer MDA-MB-231 cell line, human prostate cancer PC3 cell line, human melanoma WM9 cell line and human leukaemia HEL and K562 cell lines were evaluated. The biological result showed that those derivatives exhibited potent activities on inhibiting cancer cell growth, and the structure-activity relationships were investigated. Among them, compound 4g, which was protected by benzoyl group in 7-phenolic position and nitrified in 14-position, showed impressive inhibition on all 5 cancer cell lines, especially WM9 cell line, with an IC₅₀ value of 1.07 µM. Further mechanistic studies demonstrated that compound 4g may induce cancer cell death by apoptotic means. These research results suggested that compound 4g could be a lead for the further development toward an anticancer agent against human melanoma WM9 in the future. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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11 pages, 3007 KiB

Open AccessArticle

An Optimized Synthesis, Molecular Structure and Characterization of Benzylic Derivatives of 1,2,4-Triazin-3,5(2H,4H)-dione

by Long-Chih Hwang^1,2,*, Shiun-Yau Yang¹, Chung-Lin Chuang¹ and Gene-Hsiang Lee³

¹ Department of Medicinal and Applied Chemistry, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan

² Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

³ Instrumentation Center, College of Science, National Taiwan University, Taipei 106, Taiwan

Molecules 2017, 22(11), 1924; https://doi.org/10.3390/molecules22111924 - 8 Nov 2017

Cited by 7 | Viewed by 6174

Abstract

4-Benzyl-1,2,4-triazin-3,5(2H,4H)-dione (3-benzyl-6-azauracil, 2), and 2,4-dibenzyl-1,2,4-triazin-3,5(2H,4H)-dione (1,3-dibenzyl-6-azauracil, 3) were synthesized by the reaction of 1,2,4-triazin-3,5(2H,4H)-dione (6-azauracil, 1) with benzyl bromide and potassium carbonate in dry acetone via the 18-crown-6-ether [...] Read more.

4-Benzyl-1,2,4-triazin-3,5(2H,4H)-dione (3-benzyl-6-azauracil, 2), and 2,4-dibenzyl-1,2,4-triazin-3,5(2H,4H)-dione (1,3-dibenzyl-6-azauracil, 3) were synthesized by the reaction of 1,2,4-triazin-3,5(2H,4H)-dione (6-azauracil, 1) with benzyl bromide and potassium carbonate in dry acetone via the 18-crown-6-ether catalysis. In these reaction methods, we developed more convenient and efficient methodologies to afford compounds 2 and 3 in good yields. These compounds were characterized by ¹H- and ¹³C-NMR, MS spectrum, IR spectroscopy and elemental analysis. The structure of 2 was verified by 2D-NMR measurements, including gHSQC and gHMBC measurements. A single-crystal X-ray diffraction experiment indicated that compound 3, with the molecular formula C₁₇H₁₅N₃O₂, crystallized from a CH₃OH/CH₂Cl₂ diffusion solvent system in a monoclinic space group P2₁/c with a = 13.7844(13), b = 8.5691(8), c = 13.0527(12) Å, β = 105.961(2)°, V = 1482.3(2) Å³, Z = 4, resulting in a density D_calc of 1.314 g/cm³. The crystal structure of compound 3 is tightly stabilized by contact with five other molecules from the six short contacts formed by intermolecular C−O···H−Car, C−H···Car, and weakly π···π stacking interactions. The dihedral angle 31.90° is formed by the mean planes of the benzene rings of the N-2 and N-4 benzyl groups. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 3399 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluation of N,N-Disubstituted-4-Arylthiazole-2-Methylamine Derivatives as Cholesteryl Ester Transfer Inhibitors

by Xinran Wang^1,†, Xuehua Lin^1,†, Xuanqi Xu², Wei Li¹, Lijuan Hao¹, Chunchi Liu¹, Dongmei Zhao^1,*

and Maosheng Cheng¹

¹ Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China

² Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53715, USA

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1925; https://doi.org/10.3390/molecules22111925 - 7 Nov 2017

Cited by 9 | Viewed by 6285

Abstract

Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound 5 was discovered as a moderate CETP inhibitor. The replacement of [...] Read more.

Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N,N-substituted-4-arylthiazole-2-methylamine derivatives were designed by utilizing a conformational restriction strategy. Thirty-six compounds were synthesized and evaluated for their CETP inhibitory activities. Structure-activity relationship studies indicate that electron donor groups substituted ring A, and electron-withdrawing groups at the 4-position of ring B were critical for potency. Among these compounds, compound 30 exhibited excellent CETP inhibitory activity (IC₅₀ = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 5615 KiB

Open AccessArticle

Syntheses of Novel 4-Substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamide Derivatives with Potential Antifungal Activity

by Krzysztof Szafrański^1,*

, Jarosław Sławiński^1,*

, Anna Kędzia² and Ewa Kwapisz²

¹ Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland

² Department of Oral Microbiology, Medical University of Gdańsk, ul. Dębowa 25., 80-204, Gdańsk, Poland

Molecules 2017, 22(11), 1926; https://doi.org/10.3390/molecules22111926 - 7 Nov 2017

Cited by 17 | Viewed by 6473

Abstract

Candidiasis represent a serious threat for patients with altered immune responses. Therefore, we have undertaken the synthesis of compounds comprising a pyridine-3-sulfonamide scaffold and known antifungally active 1,2,4-triazole substituents. Thus a series of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamides have been synthesized by [...] Read more.

Candidiasis represent a serious threat for patients with altered immune responses. Therefore, we have undertaken the synthesis of compounds comprising a pyridine-3-sulfonamide scaffold and known antifungally active 1,2,4-triazole substituents. Thus a series of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamides have been synthesized by multistep reactions starting from 4-chloropyridine-3-sulfonamide via N′-cyano-N-[(4-substitutedpyridin-3-yl)sulfonyl]carbamimidothioates which were further converted with hydrazine hydrate to the corresponding 1,2,4-triazole derivatives 26–36. The final compounds were evaluated for antifungal activity against strains of the genera Candida, Geotrichum, Rhodotorula, and Saccharomycess isolated from patients with mycosis. Many of them show greater efficacy than fluconazole, mostly towards Candida albicans and Rhodotorula mucilaginosa species, with MIC values ≤ 25 µg/mL. A docking study of the most active compounds 26, 34 and 35 was performed showing the potential mode of binding to Candida albicans lanosterol 14α-demethylase. Also in vitro cytotoxicity of selected compounds have been evaluated on the NCI-60 cell line panel. Full article

(This article belongs to the Special Issue Focusing on Sulfur in Medicinal Chemistry)

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16 pages, 1125 KiB

Open AccessArticle

Chemical Fingerprint and Multicomponent Quantitative Analysis for the Quality Evaluation of Cyclocarya paliurus Leaves by HPLC–Q–TOF–MS

by Yanni Cao¹, Shengzuo Fang^1,2,*, Zhiqi Yin³, Xiangxiang Fu^1,2, Xulan Shang^1,2, Wanxia Yang^1,2 and Huimin Yang³

¹ College of Forestry, Nanjing Forestry University, Nanjing 210037, China

² Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China

³ Department of Natural Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 10009, China

Molecules 2017, 22(11), 1927; https://doi.org/10.3390/molecules22111927 - 7 Nov 2017

Cited by 64 | Viewed by 6695

Abstract

Cyclocarya paliurus is an edible and medicinal plant containing various bioactive components with significant health benefits. A combinative method using high-performance liquid chromatography (HPLC) fingerprint and quantitative analysis was developed and successfully applied for characterization and quality evaluation of C. paliurus leaves collected [...] Read more.

Cyclocarya paliurus is an edible and medicinal plant containing various bioactive components with significant health benefits. A combinative method using high-performance liquid chromatography (HPLC) fingerprint and quantitative analysis was developed and successfully applied for characterization and quality evaluation of C. paliurus leaves collected from 18 geographical locations of China. For the fingerprint analysis, 21 common peaks were observed among the 18 samples, and these peaks were identified by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC–Q–TOF–MS), while a simultaneous quantification of 16 markers was conducted to interpret the variations of contents of these bioactive compounds among the C. paliurus leaves from different geographical locations. Quantification results showed that the contents of these sixteen investigated compounds varied greatly among the leaves from different locations. The developed new method would be a valuable reference for further study and development of this bioactive plant. Full article

(This article belongs to the Section Natural Products Chemistry)

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24 pages, 5732 KiB

Open AccessArticle

Ginger and Propolis Exert Neuroprotective Effects against Monosodium Glutamate-Induced Neurotoxicity in Rats

by Usama K. Hussein^1,2, Nour El-Houda Y. Hassan³, Manal E.A. Elhalwagy⁴, Amr R. Zaki⁵, Huda O. Abubakr⁶, Kalyan C. Nagulapalli Venkata⁷, Kyu Yun Jang^2,*

and Anupam Bishayee^7,*

¹ Department of Zoology, Faculty of Science, Beni-Suef University, Beni Suef 62511, Egypt

² Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University, Hospital and Research Institute for Endocrine Sciences, Jeonju 54896, Korea

³ Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef 62511, Egypt

⁴ Faculty of Science, Al Faisaliah Campus, King Abdulaziz University, Jeddah 21453, Saudi Arabia

⁵ Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef 62511, Egypt

⁶ Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt

⁷ Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA

Molecules 2017, 22(11), 1928; https://doi.org/10.3390/molecules22111928 - 8 Nov 2017

Cited by 94 | Viewed by 11103

Abstract

Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG) neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were [...] Read more.

Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG) neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were utilized in the study. Group A served as a normal control, whereas group B was orally administered with MSG (100 mg/kg body weight, via oral gavage). Two additional groups, C and D, were given MSG as group B along with oral dose (500 mg/kg body weight) of either ginger or propolis (600 mg/kg body weight) once a day for two months. At the end, the rats were sacrificed, and the brain tissue was excised and levels of neurotransmitters, ß-amyloid, and DNA oxidative marker 8-OHdG were estimated in the brain homogenates. Further, formalin-fixed and paraffin-embedded brain sections were used for histopathological evaluation. The results showed that MSG increased lipid peroxidation, nitric oxide, neurotransmitters, and 8-OHdG as well as registered an accumulation of ß-amyloid peptides compared to normal control rats. Moreover, significant depletions of glutathione, superoxide dismutase, and catalase as well as histopathological alterations in the brain tissue of MSG-treated rats were noticed in comparison with the normal control. In contrast, treatment with ginger greatly attenuated the neurotoxic effects of MSG through suppression of 8-OHdG and β-amyloid accumulation as well as alteration of neurotransmitter levels. Further improvements were also noticed based on histological alterations and reduction of neurodegeneration in the brain tissue. A modest inhibition of the neurodegenerative markers was observed by propolis. The study clearly indicates a neuroprotective effect of ginger and propolis against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present in these natural products. Full article

(This article belongs to the Collection Herbal Medicine Research)

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38 pages, 4853 KiB

Open AccessReview

Cell-Penetrating Peptides: Design Strategies beyond Primary Structure and Amphipathicity

by Daniela Kalafatovic¹ and Ernest Giralt^1,2,*

¹ Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac, 10, 08028 Barcelona, Spain

² Department of Inorganic and Organic Chemistry, University of Barcelona, Marti i Franques, 1-5, 08028 Barcelona, Spain

Molecules 2017, 22(11), 1929; https://doi.org/10.3390/molecules22111929 - 8 Nov 2017

Cited by 247 | Viewed by 21594

Abstract

Efficient intracellular drug delivery and target specificity are often hampered by the presence of biological barriers. Thus, compounds that efficiently cross cell membranes are the key to improving the therapeutic value and on-target specificity of non-permeable drugs. The discovery of cell-penetrating peptides (CPPs) [...] Read more.

Efficient intracellular drug delivery and target specificity are often hampered by the presence of biological barriers. Thus, compounds that efficiently cross cell membranes are the key to improving the therapeutic value and on-target specificity of non-permeable drugs. The discovery of cell-penetrating peptides (CPPs) and the early design approaches through mimicking the natural penetration domains used by viruses have led to greater efficiency of intracellular delivery. Following these nature-inspired examples, a number of rationally designed CPPs has been developed. In this review, a variety of CPP designs will be described, including linear and flexible, positively charged and often amphipathic CPPs, and more rigid versions comprising cyclic, stapled, or dimeric and/or multivalent, self-assembled peptides or peptido-mimetics. The application of distinct design strategies to known physico-chemical properties of CPPs offers the opportunity to improve their penetration efficiency and/or internalization kinetics. This led to increased design complexity of new CPPs that does not always result in greater CPP activity. Therefore, the transition of CPPs to a clinical setting remains a challenge also due to the concomitant involvement of various internalization routes and heterogeneity of cells used in the in vitro studies. Full article

(This article belongs to the Special Issue Peptide-Based Drugs and Drug Delivery Systems)

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19 pages, 4699 KiB

Open AccessArticle

Preparation and Characterization of Cellulose Triacetate as Support for Lecitase Ultra Immobilization

by Francielle Batista da Silva¹

, Wilson Galvão de Morais Júnior², Cleuzilene Vieira da Silva¹, Andressa Tironi Vieira³, Antônio Carlos Ferreira Batista³, Anízio Márcio de Faria³

and Rosana Maria Nascimento Assunção^3,*

¹ Laboratory of Polymers Recycling, Chemistry Institute, Federal University of Uberlândia, Uberlândia 38408-144, MG, Brazil

² Chemical Engineering Faculty, Federal University of Uberlândia, Uberlândia 38408-144, MG, Brazil

³ Faculty of Integrated Sciences—FACIP, Federal University of Uberlândia, Ituiutaba 38304-402, MG, Brazil

Molecules 2017, 22(11), 1930; https://doi.org/10.3390/molecules22111930 - 16 Nov 2017

Cited by 17 | Viewed by 7532

Abstract

The use of polymers as supports for enzyme immobilization is a strategy that enables to remove the enzymes from a chemical reaction and improve their efficiency in catalytic processes. In this work, cellulose triacetate (CTA) was used for physical adsorption of phospholipase Lecitase [...] Read more.

The use of polymers as supports for enzyme immobilization is a strategy that enables to remove the enzymes from a chemical reaction and improve their efficiency in catalytic processes. In this work, cellulose triacetate (CTA) was used for physical adsorption of phospholipase Lecitase ultra (LU). CTA is more hydrophobic than cellulose, shows good performance in the lipases immobilization being a good candidate for immobilization of phospholipases. We investigated the immobilization of LU in CTA, the stability of the immobilized enzyme (CTA-LU) and the performance of CTA-LU using soybean oil as a substrate. LU was efficiently immobilized in CTA reaching 97.1% in 60 min of contact with an enzymatic activity of 975.8 U·g⁻¹. The CTA-LU system presents good thermal stability, being superior of the free enzyme and increase of the catalytic activity in the whole range of pH values. The difference observed for immobilized enzyme compared to free one occurs because of the interaction between the enzyme and the polymer, which stabilizes the enzyme. The CTA-LU system was used in the transesterification of soybean oil with methanol, with the production of fatty acid methyl esters. The results showed that CTA-LU is a promising system for enzymatic reactions. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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8 pages, 1289 KiB

Open AccessArticle

A New Nortriterpenoid, a Sesquiterpene and Hepatoprotective Lignans Isolated from the Fruit of Schisandra chinensis

by Fenghua Li¹, Ting Zhang², Hua Sun¹, Haifeng Gu³, Hongqing Wang¹, Xianming Su¹, Changkang Li¹, Baoming Li¹, Ruoyun Chen¹ and Jie Kang^1,*

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, China

² Institute of Medical Information & Library, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 3 Yabao Street, Beijing 100020, China

³ Beijing Institute for Drug Control, 25 Science Park Road, Changping District, Beijing 102206, China

Molecules 2017, 22(11), 1931; https://doi.org/10.3390/molecules22111931 - 10 Nov 2017

Cited by 28 | Viewed by 4925

Abstract

A new nortriterpenoid, 19(R)-hydroxyl-wuweizidilactone H (1), and a sesquiterpene, (6R)-β-chamigrenic acid (2), together with one known nortriterpenoid, wuweizidilactone H (3), and three known hepatoprotective lignans, micrantherin A (4), gomisin [...] Read more.

A new nortriterpenoid, 19(R)-hydroxyl-wuweizidilactone H (1), and a sesquiterpene, (6R)-β-chamigrenic acid (2), together with one known nortriterpenoid, wuweizidilactone H (3), and three known hepatoprotective lignans, micrantherin A (4), gomisin M₂ (5) and schizandrin (6) were isolated from the fruit of Schisandra chinensis. Their structures were elucidated by UV, IR, HRESIMS, NMR spectra and X-ray analysis. Among them, the absolute configuration of 2 was confirmed for the first time. In vitro assays, compounds 4–6 (10 μM) exhibited hepatoprotective activities (survival rate: 44%, 43% and 44%) against damage induced by N-acetyl-p-aminophenol (APAP) in human liver carcinoma (HepG2) cells. Full article

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16 pages, 1449 KiB

Open AccessReview

Anticancer and Immunogenic Properties of Cardiac Glycosides

by Naira Fernanda Zanchett Schneider¹, Claudia Cerella^2,3, Cláudia Maria Oliveira Simões¹

and Marc Diederich^3,*

¹ Programa de Pós-Graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil

² Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Hôpital Kirchberg, 9, rue Edward Steichen, 2540 Luxembourg, Luxembourg

³ Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Building 29 Room 223, 1 Gwanak-ro, Gwanak-gu 08826, Korea

Molecules 2017, 22(11), 1932; https://doi.org/10.3390/molecules22111932 - 8 Nov 2017

Cited by 105 | Viewed by 10947

Abstract

Cardiac glycosides (CGs) are natural compounds widely used in the treatment of several cardiac conditions and more recently have been recognized as potential antitumor compounds. They are known to be ligands for Na/K-ATPase, which is a promising drug target in cancer. More recently, [...] Read more.

Cardiac glycosides (CGs) are natural compounds widely used in the treatment of several cardiac conditions and more recently have been recognized as potential antitumor compounds. They are known to be ligands for Na/K-ATPase, which is a promising drug target in cancer. More recently, in addition to their antitumor effects, it has been suggested that CGs activate tumor-specific immune responses. This review summarizes the anticancer aspects of CGs as new strategies for immunotherapy and drug repositioning (new horizons for old players), and the possible new targets for CGs in cancer cells. Full article

(This article belongs to the Special Issue Cardiotonic Steroids)

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12 pages, 446 KiB

Open AccessArticle

Endotoxin-Induced Inflammation Suppresses the Effect of Melatonin on the Release of LH from the Ovine Pars Tuberalis Explants—Ex Vivo Study

by Karolina Wojtulewicz

, Dorota Tomaszewska-Zaremba

and Andrzej Przemysław Herman^*

The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 Street, 05-110 Jabłonna, Poland

Molecules 2017, 22(11), 1933; https://doi.org/10.3390/molecules22111933 - 10 Nov 2017

Cited by 12 | Viewed by 4022

Abstract

The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT). However, it was previously found [...] Read more.

The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT). However, it was previously found that the secretory activity of the pituitary may be dependent on the immune status of the animal. Therefore, this study was designed to determine the role of melatonin in the modulation of luteinizing hormone (LH) secretion from the PT explants collected from saline- and endotoxin-treated ewes in the follicular phase of the oestrous cycle. Twelve Blackhead ewes were sacrificed 3 h after injection with lipopolysaccharide (LPS; 400 ng/kg) or saline, and the PTs were collected. Each PT was cut into 4 explants, which were then divided into 4 groups: I, incubated with ‘pure’ medium 199; II, treated with gonadotropin-releasing hormone (GnRH) (100 pg/mL); III, treated with melatonin (10 nmol/mL); and IV, incubated with GnRH and melatonin. Melatonin reduced (p < 0.05) GnRH-induced secretion of LH only in the PT from saline-treated ewes. Explants collected from LPS-treated ewes were characterized by lower (p < 0.05) GnRH-dependent response in LH release. It was also found that inflammation reduced the gene expression of the GnRH receptor and the MT1 melatonin receptors in the PT. Therefore, it was shown that inflammation affects the melatonin action on LH secretion from the PT, which may be one of the mechanisms via which immune/inflammatory challenges disturb reproduction processes in animals. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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16 pages, 4111 KiB

Open AccessArticle

Natural Cyclopeptide RA-XII, a New Autophagy Inhibitor, Suppresses Protective Autophagy for Enhancing Apoptosis through AMPK/mTOR/P70S6K Pathways in HepG2 Cells

by Lihua Song^1,†

, Zhe Wang^1,†, Yurong Wang¹, Di Guo¹, Jianhong Yang², Lijuan Chen² and Ninghua Tan^1,3,*

¹ School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China

² State Key Laboratory of Biotherapy, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China

³ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1934; https://doi.org/10.3390/molecules22111934 - 11 Nov 2017

Cited by 50 | Viewed by 7206

Abstract

Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII [...] Read more.

Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII on a hepatic tumor and its underlying mechanisms in human hepatoma HepG2 cells. The results showed that RA-XII effectively inhibited the proliferation of HepG2 cells. Consistently, RA-XII significantly induced apoptosis in HepG2 cells by decreasing the expression of caspase 3, 8, 9, and promoting the Cleavage of PARP. Moreover, RA-XII-induced apoptosis was attenuated in the presence of apoptosis inhibitor N-Benzyloxycarbonyl-Val-Ala-Asp (O-Me) fluoromethyl keton, suggesting that RA-XII induced apoptosis-cell-death in HepG2 cells. Furthermore, autophagy-related proteins and mRNA levels were dramatically reduced after RA-XII treatment. Meanwhile, we observed that autophagy inhibitor chloroquine could enhance apoptosis in RA-XII-treated HepG2 cells, indicating that autophagy played a protective role in HepG2 cells and RA-XII might inhibit protective autophagy. Further analysis showed that RA-XII inhibited AMPK phosphorylation and led to the mTOR/P70S6K pathway activation, suggesting that RA-XII inhibited autophagy through AMPK/mTOR/P70S6K pathways. This study demonstrated that RA-XII promoted apoptosis and inhibited protective autophagy through AMPK/mTOR/P70S6K pathways in HepG2 cells. In conclusion, these findings suggest that RA-XII might potentially be a candidate as an autophagy inhibitor agent for further therapy of liver cancer. Full article

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14 pages, 1419 KiB

Open AccessArticle

Rapid Determination of Major Compounds in the Ethanol Extract of Geopropolis from Malaysian Stingless Bees, Heterotrigona itama, by UHPLC-Q-TOF/MS and NMR

by Lingling Zhao^1,2

, Mengjiao Yu¹, Minghui Sun¹, Xiaofeng Xue^1,*, Tongtong Wang³, Wei Cao² and Liping Sun^1,*

¹ Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China

² Institute of Analytical Science, Shaanxi Provincial Key Lab of Electroanalytical Chemistry, Northwest University, Xi’an 710069, China

³ Institute of Quality Standard and Testing Technology for Agro–Products, Beijing 100081, China

Molecules 2017, 22(11), 1935; https://doi.org/10.3390/molecules22111935 - 10 Nov 2017

Cited by 23 | Viewed by 5629

Abstract

A reliable, rapid analytical method was established for the characterization of constituents of the ethanol extract of geopropolis (EEGP) produced by Malaysian stingless bees—Heterotrigona itama—by combining ultra-high-performance liquid chromatography with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Based on known standards, the online [...] Read more.

A reliable, rapid analytical method was established for the characterization of constituents of the ethanol extract of geopropolis (EEGP) produced by Malaysian stingless bees—Heterotrigona itama—by combining ultra-high-performance liquid chromatography with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Based on known standards, the online METLIN database, and published literature, 28 compounds were confirmed. Phenolic acids, flavones, triterpenes and phytosterol were identified or tentatively identified using characteristic diagnostic fragment ions. The results indicated that terpenoids were the main components of EEGP, accompanied by low levels of phenolic acids, flavonoids, and phytosterol. Two major components were further purified by preparative high-performance liquid chromatography (PHPLC) and identified by nuclear magnetic resonance (NMR) as 24(E)-cycloart-24-ene-26-ol-3-one and 20-hydroxy-24-dammaren-3-one. These two triterpenes, confirmed in this geopropolis for the first time, are potential chemical markers for the identification of geopropolis from Malaysian stingless bees, H. itama. Full article

(This article belongs to the Section Natural Products Chemistry)

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10 pages, 2278 KiB

Open AccessArticle

Synthesis and Molecular Modeling Studies of N′-Hydroxyindazolecarboximidamides as Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors

by Dong-Ho Lee^1,2,†

, Joo-Youn Lee^3,†, Jieun Jeong¹, Miok Kim^1,4, Kyung Won Lee^1,4, Eunseo Jang¹

, Sunjoo Ahn^1,5, Chang Hoon Lee^1,4,* and Jong Yeon Hwang^1,4,5,*

¹ Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea

² Department of Chemistry, Sogang University, Seoul 121-742, Korea

³ Korea Chemical Bank, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea

⁴ Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea

⁵ Department of Medicinal Chemistry and Pharmacology, University of Science & Technology, Daejeon 34113, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1936; https://doi.org/10.3390/molecules22111936 - 9 Nov 2017

Cited by 8 | Viewed by 5987

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover [...] Read more.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N′-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme. Molecular docking studies revealed that 8a binds to IDO1 with the same binding mode as the analog, epacadostat (INCB24360). Here, we report the synthesis and biological evaluation of these hydroxyindazolecarboximidamides and present the molecular docking study of 8a with IDO1. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 14319 KiB

Open AccessArticle

Simultaneous Determination of Seven Components in Rat Plasma by the UPLC-MS/MS Method and Application of Pharmacokinetic Studies to SimiaoYong’an Decoction

by Yuanyan Liu¹, Sensen Chi¹, Weihua Wang², Lei Su¹ and Bin Liu^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, No. 6, Beijing Central South Road, Chaoyang District, Beijing 100102, China

² Chemical Metrology & Analytical Science Division, National Institute of Metrology, P.R., No. 18, EastRoad of the Third North Circle Ring, Chaoyang District, Beijing 100013, China

Molecules 2017, 22(11), 1937; https://doi.org/10.3390/molecules22111937 - 9 Nov 2017

Cited by 12 | Viewed by 4554

Abstract

SimiaoYong’an Decoction (SYD) is a classical traditional Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation. We developed a sensitive ultra-performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) method for the simultaneous determination of seven major active ingredients of [...] Read more.

SimiaoYong’an Decoction (SYD) is a classical traditional Chinese prescription that is used for the treatment of gangrene, heat-clearing, detoxification and pain alleviation. We developed a sensitive ultra-performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) method for the simultaneous determination of seven major active ingredients of SYD extract (i.e., harpagide, chlorogenic acid, sweroside, loganin, liquiritin, angoroside C and harpagoside) in rat plasma. The preliminary steps in the plasma analysis were the addition of an internal standard such as linarin, followed by protein precipitation with methanol. Separation of the active ingredients was performed on an ACQUITY UPLC^® BEH C18 column (100 mm × 2.1 mm, 1.7 μm) at a flow rate of 0.2 mL/min with methanol/water 0.1% formic acid aqueous (V/V) as the mobile phase. Detection was performed on a triple quadrupole tandem MS (QqQ-MS) via negative ion electrospray ionization in multiple reactions monitoring (MRM) mode. All calibration curves showed good linearity (r > 0.99) over the concentration range with a low limit of quantification between 0.029 and 5.813 ng/mL. Precision was evaluated by intra-day and inter-day assays, and the percentages of the RSD were all within 8.1%. The extraction efficiency and matrix effect were 80.6–113.6% and 82.9–99.5%, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of SYD extract and the corresponding single and combined traditional Chinese medicines (TCMs). The pharmacokinetic properties of the seven ingredients showed dynamic changes due to counteraction among the different coexisting components. The established approach has proven useful in the study of the active constituents in a traditional Chinese prescription. Full article

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11 pages, 1344 KiB

Open AccessArticle

An Optimized and Sensitive Pharmacokinetic Quantitative Method of Investigating Gastrodin, Parishin, and Parishin B, C and E in Beagle Dog Plasma using LC-MS/MS after Intragastric Administration of Tall Gastrodia Capsules

by Junqiu Liu^†, Sha Chen^†

, Jintang Cheng, Jun Zhang, Yuesheng Wang and An Liu^*

¹ Key laboratory of Beijing for identification and safety evaluation of Chinese medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China

^† These authors contributed equally to this paper.

Molecules 2017, 22(11), 1938; https://doi.org/10.3390/molecules22111938 - 10 Nov 2017

Cited by 10 | Viewed by 5841

Abstract

Gastrodia elata Blume, called Tianma in China, has been widely used to treat headaches, convulsions and epilepsy for thousands of years. In the present study, a series of optimizations were employed to develop a rapid, sensitive, and reliable high-performance liquid chromatography-triple quadrupole mass [...] Read more.

Gastrodia elata Blume, called Tianma in China, has been widely used to treat headaches, convulsions and epilepsy for thousands of years. In the present study, a series of optimizations were employed to develop a rapid, sensitive, and reliable high-performance liquid chromatography-triple quadrupole mass spectrometry method, which was then used for the simultaneous determination of gastrodin, parishin, parishin B, parishin C and parishin E in beagle dog plasma after intragastric administration of tall Gastrodia capsules (Tianma brand). The chromatographic separation was achieved on a C₁₈ column with gradient elution by using a mixture of 0.4% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 0.15 mL/min. A tandem mass spectrometric detection was conducted using multiple-reaction monitoring (MRM) via electrospray ionization (ESI) source in negative ionization mode. Samples were pre-treated by a single-step protein precipitation with methanol, and bergenin was used as internal standard (IS). Under the optimized conditions, the lower limit of quantification (LLOQ) was 0.10 ng/mL for gastrodin, 0.40 ng/mL for parishin B, 0.02 ng/mL for parishin E and 0.20 ng/mL for parishin and parishin C, all of which previously were the highest levels of sensitivity. The methods were optimized for selectivity, calibration curves, accuracy and precision. Extraction recoveries, matrix effects and stability were within acceptable ranges. Pharmacokinetic parameters of the tested substances were also quantitatively determined. Finally, a possible metabolic pathway was induced based on correlations obtained from quantitative and qualitative data analysis in vivo. Full article

(This article belongs to the Collection Herbal Medicine Research)

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10 pages, 353 KiB

Open AccessArticle

Disaccharides: Influence on Volatiles and Phenolics of Sour Cherry Juice

by Emil Zlatić¹, Anita Pichler² and Mirela Kopjar^2,*

¹ Biotechnical Faculty, Jamnikarjeva 101, Ljubljana 1000, Slovenia

² Faculty of Food Technology, Josip Juraj Strossmayer University in Osijek, F. Kuhača 20, Osijek 31000, Croatia

Molecules 2017, 22(11), 1939; https://doi.org/10.3390/molecules22111939 - 9 Nov 2017

Cited by 10 | Viewed by 4298

Abstract

The food industry is continuously developing ingredients, processing methods and packaging materials to improve the quality of fruit products. The aim of this work was to study the effect of sugars, a common ingredient in the food industry, on phenolics and volatiles of [...] Read more.

The food industry is continuously developing ingredients, processing methods and packaging materials to improve the quality of fruit products. The aim of this work was to study the effect of sugars, a common ingredient in the food industry, on phenolics and volatiles of sour cherry juice. Sucrose, trehalose and maltose chemical isomers were chosen for this investigation. All sugars influenced the evaluated parameters. Samples with maltose addition had lower, while samples with sucrose and trehalose addition had higher anthocyanin content than the control sample. Generally, trehalose had a higher positive effect on volatiles with the desired flavor note. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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11 pages, 986 KiB

Open AccessCommunication

Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144

by Laetitia Nivelle¹, Jane Hubert², Eric Courot³

, Nicolas Borie², Jean-Hugues Renault²

, Jean-Marc Nuzillard²

, Dominique Harakat², Christophe Clément³, Laurent Martiny¹

, Dominique Delmas⁴, Philippe Jeandet^3,*

and Michel Tarpin¹

¹ Unité Matrice Extracellulaire et Dynamique Cellulaire, UMR CNRS 7369, SFR Cap-Santé FED 4231, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France

² Institut de Chimie Moléculaire de Reims, UMR CNRS 7312, SFR Cap-Santé FED 4231, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51687 Reims CEDEX 2, France

³ Unité de Recherche Vignes et Vins de Champagne EA 4707, SFR Condorcet FR CNRS 3417, UFR des Sciences Exactes et Naturelles, Université de Reims Champagne-Ardenne, BP 1039, 51687 Reims CEDEX 2, France

⁴ Centre de Recherche Inserm U866, Université de Bourgogne, 21000 Dijon, France

Molecules 2017, 22(11), 1940; https://doi.org/10.3390/molecules22111940 - 9 Nov 2017

Cited by 17 | Viewed by 6188

Abstract

A new resveratrol dimer (1) called labruscol, has been purified by centrifugal partition chromatography of a crude ethyl acetate stilbene extract obtained from elicited grapevine cell suspensions of Vitis labrusca L. cultured in a 14-liter stirred bioreactor. One dimensional (1D) and [...] Read more.

A new resveratrol dimer (1) called labruscol, has been purified by centrifugal partition chromatography of a crude ethyl acetate stilbene extract obtained from elicited grapevine cell suspensions of Vitis labrusca L. cultured in a 14-liter stirred bioreactor. One dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) analyses including ¹H, ¹³C, heteronuclear single-quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and correlation spectroscopy (COSY) as well as high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) were used to characterize this compound and to unambiguously identify it as a new stilbene dimer, though its relative stereochemistry remained unsolved. Labruscol was recovered as a pure compound (>93%) in sufficient amounts (41 mg) to allow assessment of its biological activity (cell viability, cell invasion and apoptotic activity) on two different cell lines, including one human skin melanoma cancer cell line HT-144 and a healthy human dermal fibroblast (HDF) line. This compound induced almost 100% of cell viability inhibition in the cancer line at a dose of 100 μM within 72 h of treatment. However, at all tested concentrations and treatment times, resveratrol displayed an inhibition of the cancer line viability higher than that of labruscol in the presence of fetal bovine serum. Both compounds also showed differential activities on healthy and cancer cell lines. Finally, labruscol at a concentration of 1.2 μM was shown to reduce cell invasion by 40%, although no similar activity was observed with resveratrol. The cytotoxic activity of this newly-identified dimer is discussed. 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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7 pages, 1426 KiB

Open AccessCommunication

Unexpected Synthesis of a Bulky Bis-Pocket A₃B-Type Meso-Cyano Porphyrin

by Ze-Yu Liu¹, Mian HR Mahmood^2,3, Jian-Zhong Wu^1,*

, Shu-Bao Yang² and Hai-Yang Liu^2,*

¹ School of Chemistry and Environment, South China Normal University, Guangzhou 510006, China

² Department of Chemistry, South China University of Technology, Guangzhou 510641, China

³ Department of Chemistry, University of Education, Lahore 54770, Pakistan

Molecules 2017, 22(11), 1941; https://doi.org/10.3390/molecules22111941 - 9 Nov 2017

Cited by 8 | Viewed by 5773

Abstract

A one-pot synthesis of bulky bis-pocket A₃B-type meso-cyano porphyrin, 5-cyano-10,15,20-tris(2,4,6-triphenylphenyl)porphyrin, has been accomplished via trifluoroacetic acid (TFA) catalyzed condensation of pyrrole and 2,4,6-triphenylbenzaldehyde in an acceptable yield of about 4%. DDQ served as oxidant and the cyanating agent. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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11 pages, 1072 KiB

Open AccessReview

Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)—Chemistry, Bioavailability, and Metabolism

by Michal Bijak

Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland

Molecules 2017, 22(11), 1942; https://doi.org/10.3390/molecules22111942 - 10 Nov 2017

Cited by 339 | Viewed by 28260

Abstract

Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not [...] Read more.

Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not only the major silymarin element but is also the most active ingredient of this extract, which has been confirmed in various studies. This compound belongs to the flavonoid group known as flavonolignans. Silybin’s structure consists in two main units. The first is based on a taxifolin, the second a phenyllpropanoid unit, which in this case is conyferil alcohol. These two units are linked together into one structure by an oxeran ring. Since the 1970s, silybin has been regarded in official medicine as a substance with hepatoprotective properties. There is a large body of research that demonstrates silybin’s many other healthy properties, but there are still a lack of papers focused on its molecular structure, chemistry, metabolism, and novel form of administration. Therefore, the aim of this paper is a literature review presenting and systematizing our knowledge of the silybin molecule, with particular emphasis on its structure, chemistry, bioavailability, and metabolism. Full article

(This article belongs to the Collection Bioactive Compounds)

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9 pages, 6153 KiB

Open AccessArticle

Soft-Template Synthesis of Mesoporous Anatase TiO₂ Nanospheres and Its Enhanced Photoactivity

by Xiaojia Li¹, Mingming Zou² and Yang Wang^1,*

¹ School of Fundamental Sciences, China Medical University, Shenyang 110122, China

² Dalian National Laboratory for Clean Energy, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China

Molecules 2017, 22(11), 1943; https://doi.org/10.3390/molecules22111943 - 10 Nov 2017

Cited by 15 | Viewed by 6809

Abstract

Highly crystalline mesoporous anatase TiO₂ nanospheres with high surface area (higher than P25 and anatase TiO₂) are prepared by a soft-template method. Despite the high specific surface area, these samples have three times lower equilibrium adsorption (<2%) than Degussa P25. [...] Read more.

Highly crystalline mesoporous anatase TiO₂ nanospheres with high surface area (higher than P25 and anatase TiO₂) are prepared by a soft-template method. Despite the high specific surface area, these samples have three times lower equilibrium adsorption (<2%) than Degussa P25. The rate constant of the mesoporous anatase TiO₂ (0.024 min⁻¹) reported here is 364% higher than that of P25 (0.0066 min⁻¹), for the same catalytic loading. The results of oxidation-extraction photometry using several reactive oxygen species (ROS) scavengers indicated that mesoporous anatase TiO₂ generates more ROS than P25 under UV-light irradiation. This significant improvement in the photocatalytic performance of mesoporous spherical TiO₂ arises from the following synergistic effects in the reported sample: (i) high surface area; (ii) improved crystallinity; (iii) narrow pore wall thicknesses (ensuring the rapid migration of photogenerated carriers to the surface of the material); and (iv) greater ROS generation under UV-light. Full article

(This article belongs to the Section Photochemistry)

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12 pages, 1598 KiB

Open AccessArticle

The Blood-Brain Barrier Permeability of Six Indole Alkaloids from Uncariae Ramulus Cum Uncis in the MDCK-pHaMDR Cell Monolayer Model

by Yi-Nan Zhang, Yan-Fang Yang, Wei Xu and Xiu-Wei Yang^*

State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China

Molecules 2017, 22(11), 1944; https://doi.org/10.3390/molecules22111944 - 10 Nov 2017

Cited by 25 | Viewed by 5399

Abstract

Uncariae Ramulus Cum Uncis (URCU) is a widely used traditional Chinese medicine, and is reported to have various central nervous system effects. Alkaloids have been demonstrated to be the predominant pharmacological active components of URCU. In order to evaluate the blood-brain barrier (BBB) [...] Read more.

Uncariae Ramulus Cum Uncis (URCU) is a widely used traditional Chinese medicine, and is reported to have various central nervous system effects. Alkaloids have been demonstrated to be the predominant pharmacological active components of URCU. In order to evaluate the blood-brain barrier (BBB) permeability and transport mechanism of six typical indole alkaloids from URCU, the MDCK-pHaMDR cell monolayer model was used as an in vitro surrogate model for BBB. The samples were analyzed by high-performance liquid chromatography, and the apparent permeability coefficients (P_app) were calculated. Among the six alkaloids, isorhynchophylline (2), isocorynoxeine (4), hirsutine (5) and hirsuteine (6) showed high permeability, with P_app values at 10⁻⁵ cm/s level in bidirectional transport. For rhynchophylline (1) and corynoxeine (3), they showed moderate permeability, with P_app values from the apical (AP) side to the basolateral (BL) side at 10⁻⁶ cm/s level and efflux ratio (P_{app BL→AP}/P_{app AP→BL}) above 2. The time- and concentration-dependency experiments indicated that the main mechanism for 2, 4, 5 and 6 through BBB was passive diffusion. The efflux mechanism involved in the transports of compounds 1 and 3 could be reduced significantly by verapamil, and molecular docking screening also showed that 1 and 3 had strong bindings to P-glycoprotein. This study provides useful information for predicting the BBB permeability for 1–6, as well as better understanding of their central nervous system pharmacological activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 4569 KiB

Open AccessFeature PaperArticle

Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors

by Willem Jespers¹, Ana Oliveira¹, Rubén Prieto-Díaz², María Majellaro², Johan Åqvist¹, Eddy Sotelo²

and Hugo Gutiérrez-de-Terán^1,*

¹ Department of Cell and Molecular Biology, Uppsala University, Biomedical Centre (BMC), BOX 596, SE-751 24 Uppsala, Sweden

² Centro Singular Investigación Quimica Biologica e Materiales Moleculares (CIQUS), Departamento de Quimica Orgánica, Facultade de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain

Molecules 2017, 22(11), 1945; https://doi.org/10.3390/molecules22111945 - 10 Nov 2017

Cited by 31 | Viewed by 9335

Abstract

The four receptors that signal for adenosine, A₁, A_2A, A_2B and A₃ ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical [...] Read more.

The four receptors that signal for adenosine, A₁, A_2A, A_2B and A₃ ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical sector for decades as potential drug targets. The many crystal structures of the A_2A, and lately the A₁ ARs, allow for the use of advanced computational, structure-based ligand design methodologies. Over the last decade, we have assessed the efficient synthesis of novel ligands specifically addressed to each of the four ARs. We herein review and update the results of this program with particular focus on molecular dynamics (MD) and free energy perturbation (FEP) protocols. The first in silico mutagenesis on the A₁AR here reported allows understanding the specificity and high affinity of the xanthine-antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). On the A_2AAR, we demonstrate how FEP simulations can distinguish the conformational selectivity of a recent series of partial agonists. These novel results are complemented with the revision of the first series of enantiospecific antagonists on the A_2BAR, and the use of FEP as a tool for bioisosteric design on the A₃AR. Full article

(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)

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13 pages, 4207 KiB

Open AccessArticle

Early Response Monitoring Following Radiation Therapy by Using [¹⁸F]FDG and [¹¹C]Acetate PET in Prostate Cancer Xenograft Model with Metabolomics Corroboration

by Yi-Hsiu Chung¹, Cheng-Kun Tsai^2,5, Chiun-Chieh Wang³, Hsi-Mu Chen^4,5, Kuan-Ying Lu^4,5, Han Chiu¹, Yu-Chun Lin⁴, Tzu-Chen Yen^1,2,* and Gigin Lin^4,5,*

¹ Center for Advanced Molecular Imaging and Translation (CAMIT), Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

² Department of Nuclear Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

³ Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan

⁴ Imaging Core Lab, Department of Medical Imaging and Intervention, Institute for Radiological Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Linkou Medical Center, 5 Fuhsing Street, Guishan, Taoyuan 333, Taiwan

⁵ Clinical Metabolomics Core Lab, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan

Molecules 2017, 22(11), 1946; https://doi.org/10.3390/molecules22111946 - 10 Nov 2017

Cited by 5 | Viewed by 5050

Abstract

We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) and [¹¹C]acetate ([¹¹C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics [...] Read more.

We aim to characterize the metabolic changes associated with early response to radiation therapy in a prostate cancer mouse model by 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) and [¹¹C]acetate ([¹¹C]ACT) positron emission tomography, with nuclear magnetic resonance (NMR) metabolomics corroboration. [¹⁸F]FDG and [¹¹C]ACT PET were performed before and following irradiation (RT, 15Gy) for transgenic adenocarcinoma of mouse prostate xenografts. The underlying metabolomics alterations of tumor tissues were analyzed by using ex vivo NMR. The [¹⁸F]FDG total lesion glucose (TLG) of the tumor significant increased in the RT group at Days 1 and 3 post-irradiation, compared with the non-RT group (p < 0.05). The [¹¹C]ACT maximum standard uptake value (SUVmax) in RT (0.83 ± 0.02) and non-RT groups (0.85 ± 0.07) were not significantly different (p > 0.05). The ex vivo NMR analysis showed a 1.70-fold increase in glucose and a 1.2-fold increase in acetate in the RT group at Day 3 post-irradiation (p < 0.05). Concordantly, the expressions of cytoplasmic acetyl-CoA synthetase in the irradiated tumors was overexpressed at Day 3 post-irradiation (p < 0.05). Therefore, TLG of [¹⁸F]FDG in vivo PET images can map early treatment response following irradiation and be a promising prognostic indicator in a longitudinal preclinical study. The underlying metabolic alterations was not reflected by the [¹¹C]ACT PET. Full article

(This article belongs to the Special Issue Molecular Imaging and Treatment Monitoring of Cancer)

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13 pages, 2745 KiB

Open AccessArticle

Altering Residue 134 Confers an Increased Substrate Range of Alkylated Nucleosides to the E. coli OGT Protein

by Nadia M. Schoonhoven^1,†, Derek K. O’Flaherty^1,2,†, Francis P. McManus^1,3,†, Lauralicia Sacre¹, Anne M. Noronha¹, M. Judith Kornblatt^1,* and Christopher J. Wilds^1,*

¹ Department of Chemistry and Biochemistry, Concordia University, Montréal, QC H4B 1R6, Canada

² Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA

³ Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1948; https://doi.org/10.3390/molecules22111948 - 11 Nov 2017

Cited by 3 | Viewed by 4034

Abstract

O⁶-Alkylguanine-DNA alkyltransferases (AGTs) are proteins responsible for the removal of mutagenic alkyl adducts at the O⁶-atom of guanine and O⁴-atom of thymine. In the current study we set out to understand the role of the Ser134 residue [...] Read more.

O⁶-Alkylguanine-DNA alkyltransferases (AGTs) are proteins responsible for the removal of mutagenic alkyl adducts at the O⁶-atom of guanine and O⁴-atom of thymine. In the current study we set out to understand the role of the Ser134 residue in the Escherichia coli AGT variant OGT on substrate discrimination. The S134P mutation in OGT increased the ability of the protein to repair both O⁶-adducts of guanine and O⁴-adducts of thymine. However, the S134P variant was unable, like wild-type OGT, to repair an interstrand cross-link (ICL) bridging two O⁶-atoms of guanine in a DNA duplex. When compared to the human AGT protein (hAGT), the S134P OGT variant displayed reduced activity towards O⁶-alkylation but a much broader substrate range for O⁴-alkylation damage reversal. The role of residue 134 in OGT is similar to its function in the human homolog, where Pro140 is crucial in conferring on hAGT the capability to repair large adducts at the O⁶-position of guanine. Finally, a method to generate a covalent conjugate between hAGT and a model nucleoside using a single-stranded oligonucleotide substrate is demonstrated. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues)

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9 pages, 2324 KiB

Open AccessArticle

Elucidating Direct Photolysis Mechanisms of Different Dissociation Species of Norfloxacin in Water and Mg²⁺ Effects by Quantum Chemical Calculations

by Se Wang^*

and Zhuang Wang^*

Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, School of Environmental Science and Engineering, Nanjing University of Information Science and Technology, Nanjing 210044, China

Molecules 2017, 22(11), 1949; https://doi.org/10.3390/molecules22111949 - 11 Nov 2017

Cited by 10 | Viewed by 4867

Abstract

The study of pollution due to combined antibiotics and metals is urgently needed. Photochemical processes are an important transformation pathway for antibiotics in the environment. The mechanisms underlying the effects of metal-ion complexation on the aquatic photochemical transformation of antibiotics in different dissociation [...] Read more.

The study of pollution due to combined antibiotics and metals is urgently needed. Photochemical processes are an important transformation pathway for antibiotics in the environment. The mechanisms underlying the effects of metal-ion complexation on the aquatic photochemical transformation of antibiotics in different dissociation forms are crucial problems in science, and beg solutions. Herein, we investigated the mechanisms of direct photolysis of norfloxacin (NOR) in different dissociation forms in water and metal ion Mg²⁺ effects using quantum chemical calculations. Results show that different dissociation forms of NOR had different maximum electronic absorbance wavelengths (NOR²⁺ < NOR⁰ < NOR⁺) and showed different photolysis reactivity. Analysis of transition states (TS) and reaction activation energies (E_a) indicated NOR⁺ generally underwent loss of the piperazine ring (C10–N13 bond cleavage) and damage to piperazine ring (N13–C14 bond cleavage). For NOR²⁺, the main direct photolysis pathways were de-ethylation (N7–C8 bond cleavage) and decarboxylation (C2–C5 bond cleavage). Furthermore, the presence of Mg²⁺ changed the order of the wavelength at maximum electronic absorbance (NOR⁺-Mg²⁺ < NOR⁰-Mg²⁺ < NOR²⁺-Mg²⁺) and increased the intensities of absorbance peaks of all three dissociation species of NOR, implying that Mg²⁺ played an important role in the direct photolysis of NOR⁰, NOR⁺, and NOR²⁺. The calculated TS results indicated that the presence of Mg²⁺ increased E_a for most direct photolysis pathways of NOR, while it decreased E_a for some direct photolysis pathways such as the loss of the piperazine ring and the damage of the piperazine ring of NOR⁰ and the defluorination of NOR⁺. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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13 pages, 2661 KiB

Open AccessArticle

NeoBOMB1, a GRPR-Antagonist for Breast Cancer Theragnostics: First Results of a Preclinical Study with [⁶⁷Ga]NeoBOMB1 in T-47D Cells and Tumor-Bearing Mice

by Aikaterini Kaloudi¹, Emmanouil Lymperis¹, Athina Giarika¹, Simone Dalm², Francesca Orlandi³, Donato Barbato³, Mattia Tedesco³, Theodosia Maina¹, Marion De Jong² and Berthold A. Nock^1,*

¹ Molecular Radiopharmacy, INRASTES/NCSR “Demokritos”, 15310 Athens, Greece

² Department of Radiology, Erasmus MC, 3015 CN Rotterdam, The Netherlands

³ Advanced Accelerator Applications, 10010 Colleretto Giacosa TO, Italy

Molecules 2017, 22(11), 1950; https://doi.org/10.3390/molecules22111950 - 11 Nov 2017

Cited by 31 | Viewed by 6796

Abstract

Background: The GRPR-antagonist-based radioligands [^67/68Ga/¹¹¹In/¹⁷⁷Lu]NeoBOMB1 have shown excellent theragnostic profiles in preclinical prostate cancer models, while [⁶⁸Ga]NeoBOMB1 effectively visualized prostate cancer lesions in patients. We were further interested to explore the theragnostic potential of NeoBOMB1 [...] Read more.

Background: The GRPR-antagonist-based radioligands [^67/68Ga/¹¹¹In/¹⁷⁷Lu]NeoBOMB1 have shown excellent theragnostic profiles in preclinical prostate cancer models, while [⁶⁸Ga]NeoBOMB1 effectively visualized prostate cancer lesions in patients. We were further interested to explore the theragnostic potential of NeoBOMB1 in GRPR-positive mammary carcinoma, by first studying [⁶⁷Ga]NeoBOMB1 in breast cancer models; Methods: We investigated the profile of [⁶⁷Ga]NeoBOMB1, a [⁶⁸Ga]NeoBOMB1 surrogate, in GRPR-expressing T-47D cells and animal models; Results: NeoBOMB1 (IC₅₀s of 2.2 ± 0.2 nM) and [^natGa]NeoBOMB1 (IC₅₀s of 2.5 ± 0.2 nM) exhibited high affinity for the GRPR. At 37 °C [⁶⁷Ga]NeoBOMB1 strongly bound to the T-47D cell-membrane (45.8 ± 0.4% at 2 h), internalizing poorly, as was expected for a radioantagonist. [⁶⁷Ga]NeoBOMB1 was detected >90% intact in peripheral mouse blood at 30 min pi. In mice bearing T-47D xenografts, [⁶⁷Ga]NeoBOMB1 specifically localized in the tumor (8.68 ± 2.9% ID/g vs. 0.6 ± 0.1% ID/g during GRPR-blockade at 4 h pi). The unfavorably high pancreatic uptake could be considerably reduced (206.29 ± 17.35% ID/g to 42.46 ± 1.31% ID/g at 4 h pi) by increasing the NeoBOMB1 dose from 10 pmol to 200 pmol, whereas tumor uptake remained unaffected. Notably, tumor values did not decline from 1 to 24 h pi; Conclusions: [⁶⁷Ga]NeoBOMB1 can successfully target GRPR-positive breast cancer in animals with excellent prospects for clinical translation. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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15 pages, 994 KiB

Open AccessReview

Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis

by Roberta D’Agata¹, Maria Chiara Giuffrida² and Giuseppe Spoto^1,2,*

¹ Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, I-95125 Catania, Italy

² Consorzio Interuniversitario “Istituto Nazionale di Biostrutture e Biosistemi”, c/o Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, I-95125 Catania, Italy

Molecules 2017, 22(11), 1951; https://doi.org/10.3390/molecules22111951 - 11 Nov 2017

Cited by 93 | Viewed by 10798

Abstract

The monitoring of DNA and RNA biomarkers freely circulating in the blood constitutes the basis of innovative cancer detection methods based on liquid biopsy. Such methods are expected to provide new opportunities for a better understanding of cancer disease at the molecular level, [...] Read more.

The monitoring of DNA and RNA biomarkers freely circulating in the blood constitutes the basis of innovative cancer detection methods based on liquid biopsy. Such methods are expected to provide new opportunities for a better understanding of cancer disease at the molecular level, thus contributing to improved patient outcomes. Advanced biosensors can advance possibilities for cancer-related nucleic acid biomarkers detection. In this context, peptide nucleic acids (PNAs) play an important role in the fabrication of highly sensitive biosensors. This review provides an overview of recently described PNA-based biosensors for cancer biomarker detection. One of the most striking features of the described detection approaches is represented by the possibility to detect target nucleic acids at the ultra-low concentration with the capability to identify single-base mutations. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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12 pages, 7672 KiB

Open AccessArticle

Halogen–Metal Exchange on Bromoheterocyclics with Substituents Containing an Acidic Proton via Formation of a Magnesium Intermediate

by Qingqiang Tian, Suqin Shang, Huajun Wang, Guoqiang Shi, Zhiyao Li and Jianyong Yuan^*

Pharmacy College, Chongqing Medical University, Chongqing 400016, China

Molecules 2017, 22(11), 1952; https://doi.org/10.3390/molecules22111952 - 11 Nov 2017

Cited by 6 | Viewed by 9893

Abstract

A selective and practical bromine–metal exchange on bromoheterocyclics bearing substituents with an acidic proton under non-cryogenic conditions was developed by a simple modification of an existing protocol. Our protocol of using a combination of i-PrMgCl and n-BuLi has not only solved the problem [...] Read more.

A selective and practical bromine–metal exchange on bromoheterocyclics bearing substituents with an acidic proton under non-cryogenic conditions was developed by a simple modification of an existing protocol. Our protocol of using a combination of i-PrMgCl and n-BuLi has not only solved the problem of intermolecular quenching that often occurred when using alkyl lithium alone as the reagent for halogen–lithium exchange, but also offered a highly selective method for performing bromo–metal exchange on dibrominated arene compounds through chelation effect. Full article

(This article belongs to the Section Organometallic Chemistry)

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11 pages, 2342 KiB

Open AccessArticle

Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain

by Elkhabiry Shaban¹, Marta Świtalska², Li Wang^1,3, Ning Wang^1,4, Fan Xiu³, Ikuya Hayashi¹, Tran Anh Ngoc¹, Sachie Nagae¹, Samah El-Ghlban¹, Shiho Shimoda¹, Ahmed Abdel Aleem El Gokha⁵, Ibrahim El Tantawy El Sayed^1,5,*, Joanna Wietrzyk^2,*

and Tsutomu Inokuchi^1,*

¹ Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan

² Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12, R. Weigla Street, 53-114 Wroclaw, Poland

³ Department of Medicinal Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China

⁴ Department of Chemistry and Materials Engineering, Yingkou Institute of Technology, Yingkou 115014, China

⁵ Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koom 32511, Egypt

Molecules 2017, 22(11), 1954; https://doi.org/10.3390/molecules22111954 - 12 Nov 2017

Cited by 10 | Viewed by 4923

Abstract

Neocryptolepine, which is a kind of tetracyclic indoloquinoline alkaloid, exhibits the inhibition of topoisomerase II and shows antiproliferative activity. The present study describes the synthesis and antiproliferative evaluation of several neocryptolepine analogues carrying a branched, functionalized dibasic side chain at C11. These 2-substituted [...] Read more.

Neocryptolepine, which is a kind of tetracyclic indoloquinoline alkaloid, exhibits the inhibition of topoisomerase II and shows antiproliferative activity. The present study describes the synthesis and antiproliferative evaluation of several neocryptolepine analogues carrying a branched, functionalized dibasic side chain at C11. These 2-substituted 5-methyl-indolo[2,3-b]quinoline derivatives were prepared by nucleophilic aromatic substitution (S_NAr) of 11-chloroneocryptolepines with appropriate 1,2- and 1,3-diamines. Some of the 11-(ω-aminoalkylamino) derivatives were further transformed into 11-ureido and thioureido analogues. Many of the prepared neocryptolepine derivatives showed submicromolar antiproliferative activity against the human leukemia MV4-11 cell line. Among them, 11-(3-amino-2-hydroxy)propylamino derivatives 2h and 2k were the most cytotoxic with a mean IC₅₀ value of 0.042 μM and 0.057 μM against the MV4-11 cell line, 0.197 μM and 0.1988 μM against the A549 cell line, and 0.138 μM and 0.117 μM against the BALB/3T3 cell line, respectively. Full article

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

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15 pages, 2400 KiB

Open AccessArticle

Halogen Bonding Involving CO and CS with Carbon as the Electron Donor

by Janet E. Del Bene^1,*

, Ibon Alkorta^2,*

and José Elguero²

¹ Department of Chemistry, Youngstown State University, Youngstown, OH 44555, USA

² Instituto de Química Médica (IQM-CSIC), Juan de la Cierva, 3, E-28006 Madrid, Spain

Molecules 2017, 22(11), 1955; https://doi.org/10.3390/molecules22111955 - 12 Nov 2017

Cited by 13 | Viewed by 4677

Abstract

MP2/aug’-cc-pVTZ calculations have been carried out to investigate the halogen-bonded complexes formed when CO and CS act as electron-pair donors through C to ClF, ClNC, ClCl, ClOH, ClCN, ClCCH, and ClNH₂. CO forms only complexes stabilized by traditional halogen bonds, and [...] Read more.

MP2/aug’-cc-pVTZ calculations have been carried out to investigate the halogen-bonded complexes formed when CO and CS act as electron-pair donors through C to ClF, ClNC, ClCl, ClOH, ClCN, ClCCH, and ClNH₂. CO forms only complexes stabilized by traditional halogen bonds, and all ClY molecules form traditional halogen-bonded complexes with SC, except ClF which forms only an ion-pair complex. Ion-pair complexes are also found on the SC:ClNC and SC:ClCl surfaces. SC:ClY complexes stabilized by traditional halogen bonds have greater binding energies than the corresponding OC:ClY complexes. The largest binding energies are found for the ion-pair SC–Cl⁺:⁻Y complexes. The transition structures which connect the complex and the ion pair on SC:ClNC and SC:ClCl potential surfaces provide the barriers for inter-converting these structures. Charge-transfer from the lone pair on C to the σ-hole on Cl is the primary charge-transfer interaction stabilizing OC:ClY and SC:ClY complexes with traditional halogen bonds. A secondary charge-transfer occurs from the lone pairs on Cl to the in-plane and out-of-plane π antibonding orbitals of ClY. This secondary interaction assumes increased importance in the SC:ClNH₂ complex, and is a factor leading to its unusual structure. C–O and C–S stretching frequencies and ¹³C chemical shieldings increase upon complex formation with ClY molecules. These two spectroscopic properties clearly differentiate between SC:ClY complexes and SC–Cl⁺:⁻Y ion pairs. Spin–spin coupling constants ^1xJ(C–Cl) for OC:ClY complexes increase with decreasing distance. As a function of the C–Cl distance, ^1xJ(C–Cl) and ¹J(C–Cl) provide a fingerprint of the evolution of the halogen bond from a traditional halogen bond in the complexes, to a chlorine-shared halogen bond in the transition structures, to a covalent bond in the ion pairs. Full article

(This article belongs to the Special Issue Halogen Bonds and Beyond)

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15 pages, 1189 KiB

Open AccessArticle

Two Sulfur Glycoside Compounds Isolated from Lepidium apetalum Willd Protect NRK52e Cells against Hypertonic-Induced Adhesion and Inflammation by Suppressing the MAPK Signaling Pathway and RAAS

by Peipei Yuan^1,2, Xiaoke Zheng^1,2,*, Meng Li^1,2, Yingying Ke^1,2, Yang Fu¹, Qi Zhang¹, Xiaolan Wang^1,2 and Weisheng Feng^1,2

¹ College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China

² Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment & Chinese Medicine Development of Henan Province, Zhengzhou 450046, China

Molecules 2017, 22(11), 1956; https://doi.org/10.3390/molecules22111956 - 12 Nov 2017

Cited by 16 | Viewed by 7095

Abstract

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e [...] Read more.

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺–K⁺ ATP content in renal medulla. After treatment with cis-DG and trans-DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca²⁺ influx was inhibited, thereby reducing the secretion of transforming growth factor-β (TGFβ), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The cis-DG and trans-DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of cis-DG and trans-DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors. Full article

(This article belongs to the Collection Bioactive Compounds)

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18 pages, 1992 KiB

Open AccessArticle

The Influence of Toothpaste Containing Australian Melaleuca alternifolia Oil and Ethanolic Extract of Polish Propolis on Oral Hygiene and Microbiome in Patients Requiring Conservative Procedures

by Tomasz Piekarz¹, Anna Mertas^2,*

, Karolina Wiatrak¹, Rafał Rój³, Patryk Kownacki⁴, Joanna Śmieszek-Wilczewska⁴, Ewelina Kopczyńska¹, Maciej Wrzoł⁴

, Maria Cisowska², Ewelina Szliszka², Zenon P. Czuba², Iwona Niedzielska⁵ and Tadeusz Morawiec⁴

¹ School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Pl. Traugutta 2, 41-800 Zabrze, Poland

² Department of Microbiology and Immunology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland

³ Department of Prosthetic Dentistry, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Plac Akademicki 17, 41-902 Bytom, Poland

⁴ Department of Oral Surgery, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Pl. Akademicki 17, 41-902 Bytom, Poland

⁵ Department and Hospital of Craniomaxillofacial Surgery and Oral Surgery, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Pl. Akademicki 17, 41-902 Bytom, Poland

Molecules 2017, 22(11), 1957; https://doi.org/10.3390/molecules22111957 - 13 Nov 2017

Cited by 27 | Viewed by 7636

Abstract

The study was based on the use of a toothpaste with antiphlogistic activity, containing Australian Melaleuca alternifolia oil (tea tree oil—TTO) and ethanolic extract of Polish propolis (EEP). Fifty-one patients with varying conditions of the gingiva were divided into two groups. The study [...] Read more.

The study was based on the use of a toothpaste with antiphlogistic activity, containing Australian Melaleuca alternifolia oil (tea tree oil—TTO) and ethanolic extract of Polish propolis (EEP). Fifty-one patients with varying conditions of the gingiva were divided into two groups. The study group received the toothpaste with TTO and EEP, while the control group received the same toothpaste but without TTO and EEP. Approximal plaque index (API), simplified oral hygiene index (OHI-s) and modified sulcus bleeding index (mSBI) were assessed in three subsequent stages. During each examination, swabs were employed for microbiological inoculation. During the period of use of toothpastes with TTO and EEP, a significant reduction of the API was observed, as assessed upon the control visit after 7 days and after 28 days, compared to baseline. A statistically significant reduction of mSBI was observed after 7 and 28 days of using the toothpaste with TTO and EEP, as compared to the value upon the initial visit. Statistically significant differences in the OHI-s value were observed in the study group, which was using the active toothpaste. The use of a toothpaste containing TTO and EEP helps to maintain microbiome balance. The observed stabilisation of bacterial microflora confirms the beneficial activity of toothpaste containing EEP and TTO compared to the control group, where the lack of these substances contributed to the emergence of qualitative and quantitative changes in oral microbiome. Full article

(This article belongs to the Special Issue Natural Products Research in Australia and New Zealand)

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16 pages, 1992 KiB

Open AccessArticle

Synthesis, Spectroscopic Characterization and Antimicrobial Potential of Certain New Isatin-Indole Molecular Hybrids

by Reem I. Al-Wabli¹, Azza S. Zakaria² and Mohamed I. Attia^1,3,*

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

² Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria 21500, Egypt

³ Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), El Bohooth Street, Dokki, Giza 12622, Egypt

Molecules 2017, 22(11), 1958; https://doi.org/10.3390/molecules22111958 - 15 Nov 2017

Cited by 30 | Viewed by 7155

Abstract

Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a–n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a–n [...] Read more.

Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a–n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a–n was assessed using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against a panel of Gram-negative bacteria, Gram-positive bacteria and fungi. Most of the synthesized compounds 5a–n showed weak activities against Gram-negative bacteria while compounds 5b and 5c exhibited good activities against Gram-positive bacteria. On the other hand, compound 5j emerged as the most active compound towards Candida albicans (C. albicans), with an MIC value of 3.9 µg/mL, and compound 5g as the most active congener towards Asperagillus niger (A. niger), with an MIC value of 15.6 µg/mL. Moreover, compound 5h manifested the best anti-P. notatum effect, with an MIC value of 7.8 µg/mL, making it equipotent with compound 5g. Full article

(This article belongs to the Special Issue The Biomedical Importance of Indoles and Their Derivatives)

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13 pages, 7029 KiB

Open AccessArticle

One-Bath Pretreatment for Enhanced Color Yield of Ink-Jet Prints Using Reactive Inks

by Wei Ma^*, Kezhan Shen, Shuang Li, Meichen Zhan and Shufen Zhang^*

¹ State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116023, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1959; https://doi.org/10.3390/molecules22111959 - 13 Nov 2017

Cited by 9 | Viewed by 5685

Abstract

In order to facilely increase the color yield of ink-jet prints using reactive inks, one-bath pretreatment of cotton fabrics with pretreatment formulation containing sodium alginate, glycidyltrimethylammonium chloride (GTA), sodium hydroxide, and urea is designed for realizing sizing and cationization at the same time. [...] Read more.

In order to facilely increase the color yield of ink-jet prints using reactive inks, one-bath pretreatment of cotton fabrics with pretreatment formulation containing sodium alginate, glycidyltrimethylammonium chloride (GTA), sodium hydroxide, and urea is designed for realizing sizing and cationization at the same time. The pretreatment conditions, including the concentrations of GTA and alkali, baking temperature, and time are optimized based on the result of thecolor yield on cationic cotton for magenta ink. The mechanism for color yield enhancement on GTA-modified fabrics is discussed and the stability of GTA in the print paste is investigated. Scanning electron microscopey, tear strength, and thermogravimetric analysis of the modified and unmodified cotton are studied and compared. Using the optimal pretreatment conditions, color yield on the cationic cotton for magenta, cyan, yellow, and black reactive inks are increased by 128.7%, 142.5%, 71.0%, and 38.1%, respectively, compared with the corresponding color yield on the uncationized cotton. Much less wastewater is produced using this one-bath pretreatment method. Colorfastness of the reactive dyes on the modified and unmodified cotton is compared and boundary clarity between different colors is evaluated by ink-jet printing of colorful patterns. Full article

(This article belongs to the Special Issue Cellulose Chemical Modifications—Towards Sustainable Materials)

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21 pages, 8104 KiB

Open AccessArticle

Design, Synthesis, and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Anti-Inflammatory Agents

by Yuan Zhang^1,2,†

, Lu Luo^1,†, Chao Han¹, Handeng Lv¹, Di Chen¹, Guoliang Shen¹, Kaiqi Wu¹, Suwei Pan¹ and Faqing Ye^1,*

¹ School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China

² Department of Forensic Medicine, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China

^† These authors contribute equally to this work.

Molecules 2017, 22(11), 1960; https://doi.org/10.3390/molecules22111960 - 13 Nov 2017

Cited by 26 | Viewed by 5213

Abstract

We designed and synthesized 26 prototype compounds and studied their anti-inflammatory activity and underlying molecular mechanisms. The inhibitory effects of the compounds on the production of nitric oxide (NO), cytokines, inflammatory-related proteins, and mRNAs in lipopolysaccharide (LPS)-stimulated macrophages were determined by the Griess [...] Read more.

We designed and synthesized 26 prototype compounds and studied their anti-inflammatory activity and underlying molecular mechanisms. The inhibitory effects of the compounds on the production of nitric oxide (NO), cytokines, inflammatory-related proteins, and mRNAs in lipopolysaccharide (LPS)-stimulated macrophages were determined by the Griess assay, Enzyme linked immunosorbent assay (ELISA), Western blot analysis, and Reverse transcription-Polymerase Chain Reaction (RT-PCR), respectively. Our results indicated that treatment with A2, A6 and B7 significantly inhibited the secretion of NO and inflammatory cytokines in RAW264.7 cells without demonstrable cytotoxicity. It was also found that A2, A6 and B7 strongly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase enzyme COX-2, and prevented nuclear translocation of nuclear factor κB (NF-κB) p65 by inhibiting the degradation of p50 and IκBα. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPKs) in LPS-stimulated RAW264.7 cells was significantly inhibited by A2, A6 and B7. These findings suggest that A2, A6 and B7 may operate as an effective anti-inflammatory agent through inhibiting the activation of NF-κB and MAPK signaling pathways in macrophages. Moreover, rat paw swelling experiments showed that these compounds possess anti-inflammatory activity in vivo, with compound A6 exhibiting similar activities to the reference drug Indomethacin. Full article

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22 pages, 4481 KiB

Open AccessArticle

Effect of Structure on Charge Distribution in the Isatin Anions in Aprotic Environment: Spectral Study

by Pavol Tisovský^1,*, Róbert Šandrik¹, Miroslav Horváth¹, Jana Donovalová¹, Klaudia Jakusová¹, Marek Cigáň¹, Róbert Sokolík¹, Anton Gáplovský¹, Martin Gáplovský² and Juraj Filo¹

¹ Faculty of Natural Sciences, Institute of Chemistry, Comenius University, Ilkovičova 6, Mlynská dolina CH-2, SK-842 15 Bratislava, Slovakia

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojárov 10, SK-832 32 Bratislava, Slovakia

Molecules 2017, 22(11), 1961; https://doi.org/10.3390/molecules22111961 - 14 Nov 2017

Cited by 21 | Viewed by 6760

Abstract

Five isatin anions were prepared by deprotonation of initial isatins in aprotic solvents using basic fluoride and acetate anions (F⁻ and CH₃COO⁻). The F⁻ basicity is sufficient to deprotonate isatin NH hydrogen from all the studied compounds. [...] Read more.

Five isatin anions were prepared by deprotonation of initial isatins in aprotic solvents using basic fluoride and acetate anions (F⁻ and CH₃COO⁻). The F⁻ basicity is sufficient to deprotonate isatin NH hydrogen from all the studied compounds. This process is reversible. In the presence of proton donor solvents, the anions form the corresponding isatins. The isatin hydrogen acidity depends on the overall structure of the isatin derivatives. The anions were characterized by ultraviolet–visible (UV–Vis), Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Interestingly, the anions form aggregates at concentrations above 10⁻³ mol·dm⁻³. Further, the effect of cations on the UV–Vis spectra of the studied anions was studied. Charge transfer and its distribution in the anion depends on the radius and the cation electron configuration. The alkali metal cations, tetrabutylammonium (TBA⁺), Mg²⁺ and Ag⁺, interact with the C-2 carbonyl oxygen of the isatin anion. The interaction has a coulombic character. On the other hand, Cd²⁺, Zn²⁺, Hg²⁺, Co²⁺, and Cu⁺ cations form a coordinate bond with the isatin nitrogen. Full article

(This article belongs to the Section Physical Chemistry)

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23 pages, 2870 KiB

Open AccessReview

The killer of Socrates: Coniine and Related Alkaloids in the Plant Kingdom

by Hannu Hotti and Heiko Rischer^*

VTT Technical Research Centre of Finland Ltd., P.O. Box 1000, 02044 Espoo, Finland

Molecules 2017, 22(11), 1962; https://doi.org/10.3390/molecules22111962 - 14 Nov 2017

Cited by 57 | Viewed by 21195

Abstract

Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine’s most famous victim is Socrates who was sentenced to death [...] Read more.

Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine’s most famous victim is Socrates who was sentenced to death by poison chalice containing poison hemlock in 399 BC. In chemistry, coniine holds two historical records: It is the first alkaloid the chemical structure of which was established (in 1881), and that was chemically synthesized (in 1886). In plants, coniine and twelve closely related alkaloids are known from poison hemlock (Conium maculatum L.), and several Sarracenia and Aloe species. Recent work confirmed its biosynthetic polyketide origin. Biosynthesis commences by carbon backbone formation from butyryl-CoA and two malonyl-CoA building blocks catalyzed by polyketide synthase. A transamination reaction incorporates nitrogen from l-alanine and non-enzymatic cyclization leads to γ-coniceine, the first hemlock alkaloid in the pathway. Ultimately, reduction of γ-coniceine to coniine is facilitated by NADPH-dependent γ-coniceine reductase. Although coniine is notorious for its toxicity, there is no consensus on its ecological roles, especially in the carnivorous pitcher plants where it occurs. Lately there has been renewed interest in coniine’s medical uses particularly for pain relief without an addictive side effect. Full article

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

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11 pages, 4734 KiB

Open AccessArticle

Design, Recombinant Fusion Expression and Biological Evaluation of Vasoactive Intestinal Peptide Analogue as Novel Antimicrobial Agent

by Chunlan Xu^*, Yu Guo, Xiangjin Qiao, Xiaoya Shang, Weining Niu and Mingliang Jin^*

The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an 710072, China

Molecules 2017, 22(11), 1963; https://doi.org/10.3390/molecules22111963 - 14 Nov 2017

Cited by 12 | Viewed by 4607

Abstract

Antimicrobial peptides represent an emerging category of therapeutic agents with remarkable structural and functional diversity. Modified vasoactive intestinal peptide (VIP) (VIP analogue 8 with amino acid sequence “FTANYTRLRRQLAVRRYLAAILGRR”) without haemolytic activity and cytotoxicity displayed enhanced antimicrobial activities against Staphylococcus aureus (S. aureus [...] Read more.

Antimicrobial peptides represent an emerging category of therapeutic agents with remarkable structural and functional diversity. Modified vasoactive intestinal peptide (VIP) (VIP analogue 8 with amino acid sequence “FTANYTRLRRQLAVRRYLAAILGRR”) without haemolytic activity and cytotoxicity displayed enhanced antimicrobial activities against Staphylococcus aureus (S. aureus) ATCC 25923 and Escherichia coli (E. coli) ATCC 25922 than parent VIP even in the presence of 180 mM NaCl or 50 mM MgCl₂, or in the range of pH 4–10. VIP analogue 8 was expressed as fusion protein thioredoxin (Trx)-VIP8 in E. coli BL21(DE) at a yield of 45.67 mg/L. The minimum inhibitory concentration (MIC) of the recombinant VIP analogue 8 against S. aureus ATCC 25923 and E. coli ATCC 25922 were 2 μM. These findings suggest that VIP analogue 8 is a promising candidate for application as a new and safe antimicrobial agent. Full article

(This article belongs to the Special Issue Antimicrobial Peptides and Peptidomimetics)

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32 pages, 1809 KiB

Open AccessReview

Phospholipids of Animal and Marine Origin: Structure, Function, and Anti-Inflammatory Properties

by Ronan Lordan

, Alexandros Tsoupras

and Ioannis Zabetakis^*

Department of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland

Molecules 2017, 22(11), 1964; https://doi.org/10.3390/molecules22111964 - 14 Nov 2017

Cited by 240 | Viewed by 26455

Abstract

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: ^{Section 1} presents an overview of the relationship between structures [...] Read more.

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: ^{Section 1} presents an overview of the relationship between structures and biological activities (pro-inflammatory or anti-inflammatory) of several phospholipids with respect to inflammation. ^{Section 2} and ^{Section 3} are dedicated to the structures, functions, compositions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option because of its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed. Full article

(This article belongs to the Special Issue Phospholipids: Structure and Function)

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10 pages, 420 KiB

Open AccessArticle

Antimalarial Activity of Acetylenic Thiophenes from Echinops hoehnelii Schweinf

by Helen Bitew^1,2, Wendimagegn Mammo³, Ariaya Hymete¹ and Mariamawit Yonathan Yeshak^1,*

¹ Department of Pharmaceutical Chemistry and Pharmacognosy, School of pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa P.O. Box 9086, Ethiopia

² DDepartment of Pharmacognosy, School of Pharmacy, College of Health Sciences, Mekelle University, P.O.Box 1871, Ethiopia

³ Department of Chemistry, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa P.O. Box 1176, Ethiopia

Molecules 2017, 22(11), 1965; https://doi.org/10.3390/molecules22111965 - 21 Nov 2017

Cited by 13 | Viewed by 5119

Abstract

Malaria is one of the world’s most severe endemic diseases and due to the emergence of resistance to the currently available medicines, the need for new targets and relevant antimalarial drugs remains acute. The crude extract, four solvent fractions and two isolated compounds [...] Read more.

Malaria is one of the world’s most severe endemic diseases and due to the emergence of resistance to the currently available medicines, the need for new targets and relevant antimalarial drugs remains acute. The crude extract, four solvent fractions and two isolated compounds from the roots of Echinops hoehnelii were tested for their antimalarial activity using the standard four-day suppressive method in Plasmodium berghei-infected mice. The 80% methanol extract exhibited suppression of 4.6%, 27.8%, 68.5% and 78.7% at dose of 50, 100, 200 and 400 mg/kg respectively. The dichloromethane fraction displayed chemosuppression of 24.9, 33.5 and 43.0% dose of 100, 200 and 400 mg/kg of body weight. Five acetylenicthiophenes were isolated from the dichloromethane fraction of which 5-(penta-1,3-diynyl)-2-(3,4-dihydroxybut-1-ynyl)-thiophene decreased the level of parasitaemia by 43.2% and 50.2% while 5-(penta-1,3-diynyl)-2-(3-chloro-4-acetoxy-but-1-yn)-thiophene suppressed by 18.8% and 32.7% at 50 and 100 mg/kg, respectively. The study confirmed the traditional claim of the plant to treat malaria and could be used as a new lead for the development of antimalarial drugs. Full article

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

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11 pages, 2293 KiB

Open AccessArticle

Enantioselective Biosynthesis of l-Phenyllactic Acid by Whole Cells of Recombinant Escherichia coli

by Yibo Zhu^1,2, Ying Wang^1,3, Jiayuzi Xu¹, Jiahao Chen¹, Limei Wang^1,2 and Bin Qi^1,2,*

¹ School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu 215500, China

² Key Laboratory of Food and Biotechnology of Suzhou, Changshu Institute of Technology, Changshu 215500, China

³ College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China

Molecules 2017, 22(11), 1966; https://doi.org/10.3390/molecules22111966 - 15 Nov 2017

Cited by 25 | Viewed by 6488

Abstract

Background: l-Phenyllactic acid (l-PLA)—a valuable building block in the pharmaceutical and chemical industry—has recently emerged as an important monomer in the composition of the novel degradable biocompatible material of polyphenyllactic acid. However, both normally chemically synthesized and naturally occurring phenyllactic [...] Read more.

Background: l-Phenyllactic acid (l-PLA)—a valuable building block in the pharmaceutical and chemical industry—has recently emerged as an important monomer in the composition of the novel degradable biocompatible material of polyphenyllactic acid. However, both normally chemically synthesized and naturally occurring phenyllactic acid are racemic, and the product yields of reported l-PLA synthesis processes remain unsatisfactory. Methods: We developed a novel recombinant Escherichia coli strain, co-expressing l-lactate dehydrogenase (l-LDH) from Lactobacillus plantarum subsp. plantarum and glucose dehydrogenase (GDH) from Bacillus megaterium, to construct a recombinant oxidation/reduction cycle for whole-cell biotransformation of phenylpyruvic acid (PPA) into chiral l-PLA in an enantioselective and continuous manner. Results: During fed-batch bioconversion with intermittent PPA feeding, l-PLA yield reached 103.8 mM, with an excellent enantiomeric excess of 99.7%. The productivity of l-PLA was as high as 5.2 mM·h⁻¹ per OD₆₀₀ (optical density at 600 nm) of whole cells. These results demonstrate the efficient production of l-PLA by the one-pot biotransformation system. Therefore, this stereoselective biocatalytic process might be a promising alternative for l-PLA production. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Biotechnology and Bioengineering (6-ICBB 2017))

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13 pages, 4141 KiB

Open AccessArticle

Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

by Yiming Xu^1,†, Lichuan Wu^2,3,†, Hang Dai⁴, Mingyan Gao⁴, Haroon Ur Rashid^1,5

, Haodong Wang¹, Peng Xie¹, Xu Liu¹, Jun Jiang^1,*

and Lisheng Wang^1,*

¹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China

² Medicinal College, Guangxi University, Nanning 530004, China

³ State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University; Guilin 541000, China

⁴ College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530004, China

⁵ Department of Chemistry, Sarhad University of Science & Information Technology, Peshawar, Khyber Pakhtunkhwa 25120, Pakistan

^† These authors have contributed equally.

Molecules 2017, 22(11), 1967; https://doi.org/10.3390/molecules22111967 - 14 Nov 2017

Cited by 14 | Viewed by 4640

Abstract

Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group [...] Read more.

Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2426 KiB

Open AccessArticle

The Effects of 4′-Esterified Resveratrol Derivatives on Calcium Dynamics in Breast Cancer Cells

by Joshua A. Peterson¹, Hayden P. Doughty¹, Austin J. Eells¹, Trent A. Johnson¹, Jordan P. Hastings¹, Colton M. Crowther², Merritt B. Andrus² and Jason D. Kenealey^1,*

¹ Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, UT 84602, USA

² Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA

Molecules 2017, 22(11), 1968; https://doi.org/10.3390/molecules22111968 - 14 Nov 2017

Cited by 10 | Viewed by 4078

Abstract

Triple-negative breast cancer is a highly aggressive subtype of breast cancer. Frequently, breast cancer cells modulate their calcium signaling pathways to optimize growth. Unique calcium pathways in breast cancer cells could serve as a way to target tumorigenic cells without affecting normal tissue. [...] Read more.

Triple-negative breast cancer is a highly aggressive subtype of breast cancer. Frequently, breast cancer cells modulate their calcium signaling pathways to optimize growth. Unique calcium pathways in breast cancer cells could serve as a way to target tumorigenic cells without affecting normal tissue. Resveratrol has previously been shown to activate calcium signaling pathways. We use cell viability, single-cell calcium microscopy, and RT-PCR assays to determine the activity and mechanism of three different 4′-esterified resveratrol derivatives. We demonstrate that two of the derivatives reduce cell viability more effectively than resveratrol in MDA-MB-231 human breast cancer cells. The derivatives also activate similar pro-apoptotic calcium signaling pathways. In particular, the pivalated and butyrated resveratrol derivatives are intriguing putative chemotherapeutics because they are more effective at decreasing cell viability in vitro and inhibiting the plasma membrane Ca²⁺-ATPase, a protein that is often modulated in breast cancer. Full article

(This article belongs to the Section Natural Products Chemistry)

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26 pages, 3443 KiB

Open AccessArticle

Proline-Based Carbamates as Cholinesterase Inhibitors

by Hana Pizova^1,*

, Marketa Havelkova¹, Pavel Bobal¹, Sarka Stepankova²

, Tereza Kauerova⁴, Andrzej Bak³

, Peter Kollar⁴, Violetta Kozik⁵, Michal Oravec⁶, Ales Imramovsky⁷ and Josef Jampilek^8,*

¹ Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 612 42 Brno, Czech Republic

² Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic

³ Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland

⁴ Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 612 42 Brno, Czech Republic

⁵ Department of Synthesis Chemistry, Faculty of Mathematics, Physics and Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland

⁶ Global Change Research Institute CAS, Belidla 986/4a, 603 00 Brno, Czech Republic

⁷ Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic

⁸ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia

Molecules 2017, 22(11), 1969; https://doi.org/10.3390/molecules22111969 - 14 Nov 2017

Cited by 19 | Viewed by 5697

Abstract

Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity [...] Read more.

Series of twenty-five benzyl (2S)-2-(arylcarbamoyl)pyrrolidine-1-carboxylates was prepared and completely characterized. All the compounds were tested for their in vitro ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the selectivity of compounds to individual cholinesterases was determined. Screening of the cytotoxicity of all the compounds was performed using a human monocytic leukaemia THP-1 cell line, and the compounds demonstrated insignificant toxicity. All the compounds showed rather moderate inhibitory effect against AChE; benzyl (2S)-2-[(2-chlorophenyl)carbamoyl]pyrrolidine-1-carboxylate (IC₅₀ = 46.35 μM) was the most potent agent. On the other hand, benzyl (2S)-2-[(4-bromophenyl)-] and benzyl (2S)-2-[(2-bromophenyl)carbamoyl]pyrrolidine-1-carboxylates expressed anti-BChE activity (IC₅₀ = 28.21 and 27.38 μM, respectively) comparable with that of rivastigmine. The ortho-brominated compound as well as benzyl (2S)-2-[(2-hydroxyphenyl)carbamoyl]pyrrolidine-1-carboxylate demonstrated greater selectivity to BChE. The in silico characterization of the structure–inhibitory potency for the set of proline-based carbamates considering electronic, steric and lipophilic properties was provided using comparative molecular surface analysis (CoMSA) and principal component analysis (PCA). Moreover, the systematic space inspection with splitting data into the training/test subset was performed to monitor the statistical estimators performance in the effort to map the probability-guided pharmacophore pattern. The comprehensive screening of the AChE/BChE profile revealed potentially relevant structural and physicochemical features that might be essential for mapping of the carbamates inhibition efficiency indicating qualitative variations exerted on the reaction site by the substituent in the 3′-/4′-position of the phenyl ring. In addition, the investigation was completed by a molecular docking study of recombinant human AChE. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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12 pages, 1550 KiB

Open AccessArticle

Design, Synthesis, and Use of Peptides Derived from Human Papillomavirus L1 Protein for the Modification of Gold Electrode Surfaces by Self-Assembled Monolayers

by John Alejandro Lara Carrillo¹, Ricardo Fierro Medina², Juan Manríquez Rocha³

, Erika Bustos Bustos³, Diego Sebastián Insuasty Cepeda², Javier Eduardo García Castañeda¹

and Zuly Jenny Rivera Monroy^2,*

¹ Department of Pharmacy, Universidad Nacional de Colombia, Carrera 45 No 26-85, Building 450, Office 213, 11321 Bogotá, Colombia

² Department of Chemistry, Universidad Nacional de Colombia, Carrera 45 No 26-85, Building 450, Office 334, 11321 Bogotá, Colombia

³ Department of Research, Centro de Investigación y Desarrollo Tecnológico en Electroquímica, S.C., Parque Tecnológico Querétaro, Sanfandila, Pedro Escobedo, 76703 Querétaro, Mexico

Molecules 2017, 22(11), 1970; https://doi.org/10.3390/molecules22111970 - 14 Nov 2017

Cited by 7 | Viewed by 4549

Abstract

In order to obtain gold electrode surfaces modified with Human Papillomavirus L1 protein (HPV L1)-derived peptides, two sequences, SPINNTKPHEAR and YIK, were chosen. Both have been recognized by means of sera from patients infected with HPV. The molecules, Fc-Ahx-SPINNTKPHEAR, Ac–C–Ahx-(Fc)KSPINNTKPHEAR, Ac–C– [...] Read more.

In order to obtain gold electrode surfaces modified with Human Papillomavirus L1 protein (HPV L1)-derived peptides, two sequences, SPINNTKPHEAR and YIK, were chosen. Both have been recognized by means of sera from patients infected with HPV. The molecules, Fc-Ahx-SPINNTKPHEAR, Ac–C–Ahx-(Fc)KSPINNTKPHEAR, Ac–C–Ahx-SPINNTKPHEAR(Fc)K, C–Ahx–SPINNTKPHEAR, and (YIK)₂–Ahx–C, were designed, synthesized, and characterized. Our results suggest that peptides derived from the SPINNTKPHEAR sequence, containing ferrocene and cysteine residues, are not stable and not adequate for electrode surface modification. The surface of polycrystalline gold electrodes was modified with the peptides C-Ahx-SPINNTKPHEAR or (YIK)₂-Ahx-C through self-assembly. The modified polycrystalline gold electrodes were characterized via infrared spectroscopy and electrochemical measurements. The thermodynamic parameters, surface coverage factor, and medium pH effect were determined for these surfaces. The results indicate that surface modification depends on the peptide sequence (length, amino acid composition, polyvalence, etc.). The influence of antipeptide antibodies on the voltammetric response of the modified electrode was evaluated by comparing results obtained with pre-immune and post-immune serum samples. Full article

(This article belongs to the Special Issue Supramolecular Chemistry and Self-Assembly: Themed Issue in Honor of Professor Itamar Willner on the Occasion of His 70th Birthday)

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10 pages, 1311 KiB

Open AccessArticle

Practical and Sustainable Synthesis of Optically Pure Levocabastine, a H₁ Receptor Antagonist

by Sung Kwon Kang^1,2, Dong Hyuk Nam², Jaeseung Ahn², Jaemin Lee², Jaehoon Sim¹, Jeeyeon Lee¹ and Young-Ger Suh^1,3,*

¹ College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea

² Department of Synthetic Chemistry, Chong Kun Dang Research Institute, 315-20, Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Korea

³ College of Pharmacy, Cha University, 120 Haeryong-ro, Pocheon 11160, Gyeonggi-do, Korea

Molecules 2017, 22(11), 1971; https://doi.org/10.3390/molecules22111971 - 15 Nov 2017

Cited by 1 | Viewed by 5952

Abstract

A practical and sustainable method for the synthesis of levocabastine hydrochloride (1), a H₁ receptor antagonist for the treatment of allergic conjunctivitis, that can be applied to the industrial production of the compound has been developed. Substantial improvements over the [...] Read more.

A practical and sustainable method for the synthesis of levocabastine hydrochloride (1), a H₁ receptor antagonist for the treatment of allergic conjunctivitis, that can be applied to the industrial production of the compound has been developed. Substantial improvements over the previously reported procedure are achieved via efficient preparation of an optically active key intermediate (5) without chiral resolution and with a more effective detosylation, which complements the previous procedure. Notably, our process requires no chromatographic purification and provides levocabastine hydrochloride in greater than 99.5% purity in a 14.2% overall yield. Full article

(This article belongs to the Section Organic Chemistry)

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15 pages, 2786 KiB

Open AccessArticle

An Efficient Approach for Lipase-Catalyzed Synthesis of Retinyl Laurate Nutraceutical by Combining Ultrasound Assistance and Artificial Neural Network Optimization

by Shang-Ming Huang¹, Hsin-Ju Li², Yung-Chuan Liu², Chia-Hung Kuo^3,*

and Chwen-Jen Shieh^1,*

¹ Biotechnology Center, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan

² Department of Chemical Engineering, National Chung Hsing University, 250 Kuo-Kuang Road, Taichung 40227, Taiwan

³ Department of Seafood Science, National Kaohsiung Marine University, 142 Haijhuan Road, Nanzih District, Kaohsiung 81143, Taiwan

Molecules 2017, 22(11), 1972; https://doi.org/10.3390/molecules22111972 - 15 Nov 2017

Cited by 19 | Viewed by 4325

Abstract

Although retinol is an important nutrient, retinol is highly sensitive to oxidation. At present, some ester forms of retinol are generally used in nutritional supplements because of its stability and bioavailability. However, such esters are commonly synthesized by chemical procedures which are harmful [...] Read more.

Although retinol is an important nutrient, retinol is highly sensitive to oxidation. At present, some ester forms of retinol are generally used in nutritional supplements because of its stability and bioavailability. However, such esters are commonly synthesized by chemical procedures which are harmful to the environment. Thus, this study utilized a green method using lipase as a catalyst with sonication assistance to produce a retinol derivative named retinyl laurate. Moreover, the process was optimized by an artificial neural network (ANN). First, a three-level-four-factor central composite design (CCD) was employed to design 27 experiments, which the highest relative conversion was 82.64%. Further, the optimal architecture of the CCD-employing ANN was developed, including the learning Levenberg-Marquardt algorithm, the transfer function (hyperbolic tangent), iterations (10,000), and the nodes of the hidden layer (6). The best performance of the ANN was evaluated by the root mean squared error (RMSE) and the coefficient of determination (R²) from predicting and observed data, which displayed a good data-fitting property. Finally, the process performed with optimal parameters actually obtained a relative conversion of 88.31% without long-term reactions, and the lipase showed great reusability for biosynthesis. Thus, this study utilizes green technology to efficiently produce retinyl laurate, and the bioprocess is well established by ANN-mediated modeling and optimization. Full article

(This article belongs to the Special Issue Lipases and Lipases Modification)

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12 pages, 522 KiB

Open AccessArticle

Capillary Electrophoresis Hyphenated with Mass Spectrometry for Determination of Inflammatory Bowel Disease Drugs in Clinical Urine Samples

by Katarína Maráková^1,2, Juraj Piešťanský^1,2, Zuzana Zelinková³ and Peter Mikuš^1,2,*

¹ Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia

² Toxicological and Antidoping Center (TAC), Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia

³ Department of Gastroenterology, St Michael’s Hospital, Satinského 1, SK-811 08 Bratislava, Slovakia

Molecules 2017, 22(11), 1973; https://doi.org/10.3390/molecules22111973 - 15 Nov 2017

Cited by 12 | Viewed by 4665

Abstract

Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a [...] Read more.

Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE) hyphenated with tandem mass spectrometry (MS/MS) for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine) as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol). The optimized CE-MS/MS conditions provided a very efficient and stable system for the separation and sensitive detection of these drugs in human urine matrices. The developed method was successfully applied for the assay of the targeted drugs and their selected metabolites in urine samples collected from patients suffering from inflammatory bowel disease (IBD) and receiving azathioprine therapy. The developed CE-MS/MS method, due to its reliability, short analysis time, production of complex clinical profiles, and favorable performance parameters, evaluated according to FDA guidelines for bioanalytical method validation, is proposed for routine clinical laboratories to optimize thiopurine therapy, estimate enzymatic activity, and control patient compliance with medication and co-medication. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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14 pages, 2475 KiB

Open AccessArticle

Larix decidua Bark as a Source of Phytoconstituents: An LC-MS Study

by Valeria Baldan^1,2, Stefania Sut¹, Marta Faggian³, Elena Dalla Gassa¹, Sara Ferrari², Gabriele De Nadai², Stefano Francescato², Gianni Baratto² and Stefano Dall’Acqua^1,*

¹ Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy

² Unifarco spa, Via Cal Longa 62, Santa Giustina 32035 Belluno, Italy

³ Unired srl, Via N. Tommaseo 69, 35131 Padova, Italy

Molecules 2017, 22(11), 1974; https://doi.org/10.3390/molecules22111974 - 15 Nov 2017

Cited by 21 | Viewed by 5501

Abstract

Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of [...] Read more.

Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of larch bark was performed using mixtures of ethanol/water. Furthermore, the phytochemical composition of larch bark extract was studied using LC-MSⁿ methods and the main constituents were identified as flavonoids, spiro-polyphenols, and procyanidins. To confirm the identification by LC-MS semi-preparative HPLC was performed in order to isolate the main constituents and verify the structures by ¹H-NMR. Antioxidant properties were studied using an in vitro approach combining DPPH assay and LC-MS in order to establish different roles of the various classes of phytochemicasl of the extract. DPPH activity of some of the isolated compounds was also assessed. The overall results indicate this waste material as a good source of antioxidant compounds, mainly procyanidins, whichresulted the most active constituents in the DPPH assay. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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23 pages, 4671 KiB

Open AccessArticle

Chitosan/Cyclodextrin/TPP Nanoparticles Loaded with Quercetin as Novel Bacterial Quorum Sensing Inhibitors

by Hao Thanh Nguyen^1,2 and Francisco M. Goycoolea^1,3,*

¹ Institute for Biology and Biotechnology of Plants, University of Münster, Schlossgarten 3, 48149 Münster, Germany

² Department of Biology, Faculty of Biotechnology, Vietnam National University of Agriculture, Ngo Xuan Quang Street, Hanoi 100000, Vietnam

³ School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK

Molecules 2017, 22(11), 1975; https://doi.org/10.3390/molecules22111975 - 15 Nov 2017

Cited by 43 | Viewed by 7465

Abstract

The widespread emergence of antibiotic-resistant bacteria has highlighted the urgent need of alternative therapeutic approaches for human and animal health. Targeting virulence factors that are controlled by bacterial quorum sensing (QS), seems a promising approach. The aims of this study were to generate [...] Read more.

The widespread emergence of antibiotic-resistant bacteria has highlighted the urgent need of alternative therapeutic approaches for human and animal health. Targeting virulence factors that are controlled by bacterial quorum sensing (QS), seems a promising approach. The aims of this study were to generate novel nanoparticles (NPs) composed of chitosan (CS), sulfo-butyl-ether-β-cyclodextrin (Captisol^®) and/or pentasodium tripolyphosphate using ionotropic gelation technique, and to evaluate their potential capacity to arrest QS in bacteria. The resulting NPs were in the size range of 250–400 nm with CS_70/5 and 330–600 nm with CS_70/20, had low polydispersity index (<0.25) and highly positive zeta potential ranging from ζ ~+31 to +40 mV. Quercetin, a hydrophobic model flavonoid, could be incorporated proportionally with increasing amounts of Captisol^® in the NPs formualtion, without altering significantly its physicochemical properties. Elemental analysis and FTIR studies revealed that Captisol^® and quercetin were effectively integrated into the NPs. These NPs were stable in M9 bacterial medium for 7 h at 37 °C. Further, NPs containing Captisol^® seem to prolong the release of associated drug. Bioassays against an E. coli Top 10 QS biosensor revealed that CS_70/5 NPs could inhibit QS up to 61.12%, while CS_70/20 NPs exhibited high antibacterial effects up to 88.32%. These results suggested that the interaction between NPs and the bacterial membrane could enhance either anti-QS or anti-bacterial activities. Full article

(This article belongs to the Special Issue Selected Papers from the 13th International Conference of the European Chitin Society – 8th Simposio de la Sociedad Iberoamericana de Quitina (EUCHIS-SIAQ 2017))

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11 pages, 1679 KiB

Open AccessArticle

Development of Gallic Acid-Modified Hydrogels Using Interpenetrating Chitosan Network and Evaluation of Their Antioxidant Activity

by Byungman Kang^1,†, Temmy Pegarro Vales^2,3,†

, Byoung-Ki Cho⁴, Jong-Ki Kim^5,* and Ho-Joong Kim^2,*

¹ Nuclear Chemistry Research Division, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 34057, Korea

² Department of Chemistry, Chosun University, Gwangju 61452, Korea

³ Department of Natural Sciences, Caraga State University, Butuan City 8600, Philippines

⁴ Department of Chemistry, Dankook University, 119, Dandae-ro, Chungnam 31116, Korea

⁵ Department of Biomedical Engineering, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea

^† These authors equally contributed to this work.

Molecules 2017, 22(11), 1976; https://doi.org/10.3390/molecules22111976 - 15 Nov 2017

Cited by 50 | Viewed by 11914

Abstract

In this work, antioxidant hydrogels were prepared by the construction of an interpenetrating chitosan network and functionalization with gallic acid. The poly(2-hydroxyethyl methacrylate) p(HEMA)-based hydrogels were first synthesized and subsequently surface-modified with an interpenetrating polymer network (IPN) structure prepared with methacrylamide chitosan via [...] Read more.

In this work, antioxidant hydrogels were prepared by the construction of an interpenetrating chitosan network and functionalization with gallic acid. The poly(2-hydroxyethyl methacrylate) p(HEMA)-based hydrogels were first synthesized and subsequently surface-modified with an interpenetrating polymer network (IPN) structure prepared with methacrylamide chitosan via free radical polymerization. The resulting chitosan-IPN hydrogels were surface-functionalized with gallic acid through an amide coupling reaction, which afforded the antioxidant hydrogels. Notably, gallic-acid-modified hydrogels based on a longer chitosan backbone exhibited superior antioxidant activity than their counterpart with a shorter chitosan moiety; this correlated to the amount of gallic acid attached to the chitosan backbone. Moreover, the surface contact angles of the chitosan-modified hydrogels decreased, indicating that surface functionalization of the hydrogels with chitosan-IPN increased the wettability because of the presence of the hydrophilic chitosan network chain. Our study indicates that chitosan-IPN hydrogels may facilitate the development of applications in biomedical devices and ophthalmic materials. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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12 pages, 1679 KiB

Open AccessArticle

Anti-Inflammatory Potential of 1-Nitro-2-Phenylethylene

by Michelle A. Sugimoto¹, Márcia De Jesus Amazonas da Silva², Larissa Froede Brito¹, Rosivaldo Dos Santos Borges³, Flávio Almeida Amaral⁴

, Ana Paula De Araujo Boleti³, Maritza Echevarria Ordoñez³, Jose Carlos Tavares⁵, Lirlandia Pires Sousa¹ and Emerson Silva Lima^2,*

¹ Laboratory of Inflammation Signaling, Department of Clinical Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil

² Laboratory of Biological Activity, Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus 69067-005, AM, Brazil

³ Nucleus of Studies and Selection of Bioactive Molecules, Institute of Health Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil

⁴ Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil

⁵ Laboratory of Research in Drugs, Department of Biological Sciences and Health, Federal University of Amapá, Macapá 68903-419, AP, Brazil

Molecules 2017, 22(11), 1977; https://doi.org/10.3390/molecules22111977 - 15 Nov 2017

Cited by 8 | Viewed by 4951

Abstract

Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome [...] Read more.

Inflammation is a reaction of the host to infectious or sterile stimuli and has the physiological purpose of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation can lead to tissue damage, giving rise to a plethora of chronic inflammatory diseases, including metabolic syndrome and autoimmunity pathologies with eventual loss of organ function. Beta-nitrostyrene and its derivatives are known to have several biological activities, including anti-edema, vasorelaxant, antiplatelet, anti-inflammatory, and anticancer. However, few studies have been carried out regarding the anti-inflammatory effects of this class of compounds. Thereby, the aim of this study was to evaluate the anti-inflammatory activity of 1-nitro-2-phenylethene (NPe) using in vitro and in vivo assays. Firstly, the potential anti-inflammatory activity of NPe was evaluated by measuring TNF-α produced by human macrophages stimulated with lipopolysaccharide (LPS). NPe at non-toxic doses opposed the inflammatory effects induced by LPS stimulation, namely production of the inflammatory cytokine TNF-α and activation of NF-κB and ERK pathways (evaluated by phosphorylation of inhibitor of kappa B-alpha [IκB-α] and extracellular signal-regulated kinase 1/2 [ERK1/2], respectively). In a well-established model of acute pleurisy, pretreatment of LPS-challenged mice with NPe reduced neutrophil accumulation in the pleural cavity. This anti-inflammatory effect was associated with reduced activation of NF-κB and ERK1/2 pathways in NPe treated mice as compared to untreated animals. Notably, NPe was as effective as dexamethasone in both, reducing neutrophil accumulation and inhibiting ERK1/2 and IκB-α phosphorylation. Taken together, the results suggest a potential anti-inflammatory activity for NPe via inhibition of ERK1/2 and NF-κB pathways on leukocytes. Full article

(This article belongs to the Special Issue Anti-inflammatory Agents)

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11 pages, 1888 KiB

Open AccessArticle

Predict the Relationship between Gene and Large Yellow Croaker’s Economic Traits

by Xiangxiang Zeng^1,†, Shuting Jin^1,†, Jing Jiang¹, Kunhuang Han², Xiaoping Min^1,* and Xiangrong Liu^1,*

¹ School of Information Science and Technology, Xiamen University, Xiamen 361005, China

² State Key Laboratory of Large Yellow Croaker Breeding, Ningde Fufa Fisheries Company Limited, Ningde 352000, China

^† X.Z. and S.J. contribute equally to the work.

Molecules 2017, 22(11), 1978; https://doi.org/10.3390/molecules22111978 - 16 Nov 2017

Cited by 6 | Viewed by 4273

Abstract

The importance of a gene’s impact on traits is well appreciated. Gene expression will affect the growth, immunity, reproduction and environmental resistance of some fish, and then affect the economic performance of fish-related business. Studying the connection between gene and character can help [...] Read more.

The importance of a gene’s impact on traits is well appreciated. Gene expression will affect the growth, immunity, reproduction and environmental resistance of some fish, and then affect the economic performance of fish-related business. Studying the connection between gene and character can help elucidate the growth of fishes. Thus far, a collected database containing large yellow croaker (Larimichthys crocea) genes does not exist. The gene having to do with the growth efficiency of fish will have a huge impact on research. For example, the protein encoded by the IFIH1 gene is associated with the function of viral infection in the immune system, which affects the survival rate of large yellow croakers. Thus, we collected data through the published literature and combined them with a biological genetic database related to the large yellow croaker. Based on the data, we can predict new gene–trait associations which have not yet been discovered. This work will contribute to research on the growth of large yellow croakers. Full article

(This article belongs to the Special Issue Computational Analysis for Protein Structure and Interaction)

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10 pages, 519 KiB

Open AccessArticle

Design, Synthesis and Preliminary Biological Evaluation of Novel Benzyl Sulfoxide 2-Indolinone Derivatives as Anticancer Agents

by Lin Tang, Tao Peng, Gang Wang, Xiaoxue Wen, Yunbo Sun, Shouguo Zhang^*, Shuchen Liu^* and Lin Wang^*

Beijing Institute of Radiation Medicine, Beijing 100850, China

Molecules 2017, 22(11), 1979; https://doi.org/10.3390/molecules22111979 - 16 Nov 2017

Cited by 14 | Viewed by 3800

Abstract

In this work, a series of novel benzyl sulfoxide 2-indolinone derivatives was designed and synthesized as potent anticancer agents. Tyrosine kinase inhibitory activity assay indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was further [...] Read more.

In this work, a series of novel benzyl sulfoxide 2-indolinone derivatives was designed and synthesized as potent anticancer agents. Tyrosine kinase inhibitory activity assay indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was further investigated against five human cancer cell lines (HeLa, HepG2, MCF-7, SCC-15, and A549). Several compounds exhibited evident activities. Among them, (Z)-3-(((4-bromobenzyl)sulfinyl)methylene)indolin-2-one (6j) and (Z)-3-((benzylsulfinyl)methylene)-5-bromoindolin-2-one (6o) were found to be effective tyrosine kinase inhibitors (IC₅₀ = 1.34 and 2.69 μM, respectively) in addition to having noteworthy antitumor potential (the average IC₅₀ value of 6j or 6o was less than 40 μM). This class of novel derivatives has promising potential for further development as anticancer agents. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2977 KiB

Open AccessArticle

Chitosan Spray-Dried Microparticles for Controlled Delivery of Venlafaxine Hydrochloride

by Inmaculada Aranaz¹

, Ines Paños¹, Carlos Peniche²

, Ángeles Heras¹ and Niuris Acosta^1,*

¹ Department of Physical Chemistry II. Pharmacy Faculty, Biofuncional Studies Institute, Complutense University, Paseo Juan XXIII, 1, 28040 Madrid, Spain

² Center of Biomaterials, University of Havana Ave. Universidad s/n entre G y Ronda, Vedado, 10400 La Habana, Cuba

Molecules 2017, 22(11), 1980; https://doi.org/10.3390/molecules22111980 - 15 Nov 2017

Cited by 52 | Viewed by 5935

Abstract

Venlafaxine controlled drug delivery systems using different matrixes have been tested to reduce undesirable side effects in the treatment of depression. The legal status of chitosan (Cs) in Pharmacy has dramatically improved after its acceptance as excipient in several Pharmacopeias and, therefore, there [...] Read more.

Venlafaxine controlled drug delivery systems using different matrixes have been tested to reduce undesirable side effects in the treatment of depression. The legal status of chitosan (Cs) in Pharmacy has dramatically improved after its acceptance as excipient in several Pharmacopeias and, therefore, there is great interest in pharmaceutical formulations based on this polymer. In this paper, chitosan microcapsules cross-linked with sodium tripolyphosphate (TPP) for oral delivery of venlafaxine were formulated using the spray drying technique. The effect of chitosan physico-chemical properties, TPP concentration and TPP/Cs ratio on drug release was evaluated. The microcapsules were characterized in terms of size, zeta potential and morphology. The physical state of the drug was determined by X-ray diffraction (XRD) and the drug release from the microcapsules was studied in simulated gastric and intestinal fluids. The release pattern fitted well to the Peppas-Koersmeyer model with n exponents indicating anomalous transport. Full article

(This article belongs to the Special Issue Selected Papers from the 13th International Conference of the European Chitin Society – 8th Simposio de la Sociedad Iberoamericana de Quitina (EUCHIS-SIAQ 2017))

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8 pages, 869 KiB

Open AccessArticle

Oleanane-Type Saponins from the Roots of Ligulariopsis shichuana and Their α-Glucosidase Inhibitory Activities

by Hai-Bo Wu¹, Ting-Ting Liu^1,2, Wen-Shu Wang^1,*, Jin-Chao Feng¹ and Hong-Mei Tian¹

¹ College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China

² State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Molecules 2017, 22(11), 1981; https://doi.org/10.3390/molecules22111981 - 17 Nov 2017

Cited by 7 | Viewed by 3964

Abstract

Five new oleanane-type saponins, named ligushicosides A-E, and three known oleanane-type saponins were isolated from the roots of Ligulariopsis shichuana. Their structures were established by a combination of spectroscopic techniques, including 1D and 2D NMR and high resolution electrospray ionization mass spectroscopy [...] Read more.

Five new oleanane-type saponins, named ligushicosides A-E, and three known oleanane-type saponins were isolated from the roots of Ligulariopsis shichuana. Their structures were established by a combination of spectroscopic techniques, including 1D and 2D NMR and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Furthermore, all isolates were evaluated for their yeast α-glucosidase inhibitory effects and exhibited potent inhibition against α-glucosidase, while compounds 1 and 2 showed excellent inhibitory activities. The 3-O-glycoside moiety in oleanane-type saponin is important for the α-glucosidase inhibitory effects. Full article

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11 pages, 2098 KiB

Open AccessArticle

Effect of Abscisic Acid on Accumulation of Five Active Components in Root of Glycyrrhiza uralensis

by Jing Qiao¹, Zuliang Luo¹, Yanpeng Li², Guangxi Ren², Chunsheng Liu² and Xiaojun Ma^1,*

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193, China

² College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 6 Wangjing Zhonghuan Road, Beijing 100102, China

Molecules 2017, 22(11), 1982; https://doi.org/10.3390/molecules22111982 - 15 Nov 2017

Cited by 28 | Viewed by 6659

Abstract

Licorice is one of the most generally used herbal medicines in the world; however, wild licorice resources have decreased drastically. Cultivated Glycyrrhiza uralensis Fischer are the main source of licorice at present, but the content of main active components in cultivated G. uralensis [...] Read more.

Licorice is one of the most generally used herbal medicines in the world; however, wild licorice resources have decreased drastically. Cultivated Glycyrrhiza uralensis Fischer are the main source of licorice at present, but the content of main active components in cultivated G. uralensis are lower than in wild G. uralensis. Therefore, the production of high-quality cultivated G. uralensis is an urgent issue for the research and production fields. In this study, the content of five active components and seven endogenous phytohormones in cultivated G. uralensis (two-year-old) were determined by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, different concentrations (25–200 mg/L) of exogenous abscisic acid (ABA) were sprayed on the leaves of G. uralensis in the fast growing period. Results showed that ABA, zeatin riboside (ZR), and dihydrozeatin riboside (DHZR) had strong correlation with active components. In addition, the content of five active components increased remarkably after ABA treatment. Our results indicate that ABA is significantly related to the accumulation of active components in G. uralensis, and the application of exogenous ABA at the proper concentration is able to promote the accumulation of main components in G. uralensis. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1917 KiB

Open AccessArticle

Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes

by Kateřina Lněničková

, Andrea Dymáková, Barbora Szotáková

and Iva Boušová^*

Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 50005 Hradec Králové, Czech Republic

Molecules 2017, 22(11), 1983; https://doi.org/10.3390/molecules22111983 - 16 Nov 2017

Cited by 12 | Viewed by 4937

Abstract

Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but [...] Read more.

Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer. In our study, SFN alone did not significantly alter the activity and expression of the studied DMEs, except for the glutathione S-transferase (GSTA1) mRNA level, which was significantly enhanced. Co-treatment of hepatocytes with SFN and BNF led to a substantial increase in sulfotransferase, aldoketoreductase 1C, carbonylreductase 1 and NAD(P)H:quinone oxidoreductase 1 activity and a marked decrease in cytochrome P450 (CYP) Cyp1a1, Cyp2b and Cyp3a4 expression in comparison to the treatment with BNF alone. Sulforaphane is able to modulate the activity and/or expression of DMEs, thus shifting the balance of carcinogen metabolism toward deactivation, which could represent an important mechanism of its chemopreventive activity. Full article

(This article belongs to the Collection Herbal Medicine Research)

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13 pages, 2303 KiB

Open AccessArticle

Genomic Analysis of the ASMT Gene Family in Solanum lycopersicum

by Weicheng Liu^1,†, Dake Zhao^2,†

, Chunfang Zheng^1,*, Chen Chen¹, Xin Peng¹, Yuan Cheng³ and Hongjian Wan^3,*

¹ Zhengjiang Key Laboratory of Exploitation and Preservation of Coastal Bio-Resource, Zhejiang Mariculture Research Institute, Wenzhou 325000, China

² Laboratory of Ecology and Evolutionary Biology, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan University, Kunming 650091, China

³ Statekey Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Vegetables, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1984; https://doi.org/10.3390/molecules22111984 - 16 Nov 2017

Cited by 31 | Viewed by 5905

Abstract

Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the [...] Read more.

Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the integration of the structural features, phylogenetic relationships, exon/intron configuration, and expression profile during growth and development, as well as biotic stresses. The results revealed that the tomato genome encoded a minimum of 14 members, containing three probable encoded pseudogenes. Chromosome mapping indicated that the family had probably expanded via tandem duplication events. Genome-wide RNA-seq and qRT-PCR based gene expression analysis revealed that almost half of the SlASMT genes were expressed in at least one of the experimental stages studied and also showed differential accumulation. Furthermore, the tandem duplicated SlASMT genes showed differential expression levels, which indicated probable functional divergence during the course of the evolution. Finally, this study also determined that some SlASMT genes were induced by multiple pathogens. The results suggested that these genes could be involved in tomato plant response to biotic stresses. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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10 pages, 2031 KiB

Open AccessArticle

Characterization of Non-Derivatized Cellulose Samples by Size Exclusion Chromatography in Tetrabutylammonium Fluoride/Dimethylsulfoxide (TBAF/DMSO)

by Jérémy Rebière^1,2, Antoine Rouilly¹

, Vanessa Durrieu^1,*

and Frédéric Violleau²

¹ Laboratoire de Chimie Agro-industrielle (LCA), Université de Toulouse, INRA, INPT, 31030 Toulouse, France

² Laboratoire de Chimie Agro-industrielle (LCA), Université de Toulouse, INRA, INPT, INP-EI PURPAN, 31062 Toulouse, France

Molecules 2017, 22(11), 1985; https://doi.org/10.3390/molecules22111985 - 16 Nov 2017

Cited by 8 | Viewed by 5564

Abstract

This paper deals with the use of tetrabutylammonium fluoride/dimethylsulfoxide (TBAF/DMSO) to characterize the molar mass distribution of non-derivatized cellulosic samples by size exclusion chromatography (SEC). Different cellulose samples with various average degree of polymerization (DP) were first solubilized in this solvent system, with [...] Read more.

This paper deals with the use of tetrabutylammonium fluoride/dimethylsulfoxide (TBAF/DMSO) to characterize the molar mass distribution of non-derivatized cellulosic samples by size exclusion chromatography (SEC). Different cellulose samples with various average degree of polymerization (DP) were first solubilized in this solvent system, with increasing TBAF rates, and then analyzed by SEC coupled to a refractive index detector (RID), using DMSO as mobile phase. The Molar Masses (MM) obtained by conventional calibration were then discussed and compared with suppliers’ data and MM determined by viscosimetry measurements. By this non-classic method, molar mass of low DP samples (Avicel^® and cotton fibers) have been determined. For high DP samples (α-cellulose and Vitacel^®), dissolution with TBAF concentration of 10 mg/mL involved elution of cellulose aggregates in the exclusion volume, related to an incomplete dissolution or the dilution of TBAF molecules in elution solvent, preventing the correct evaluation of their molar mass. Full article

(This article belongs to the Special Issue Natural Polymers and Biopolymers)

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35 pages, 5807 KiB

Open AccessReview

Critical Review on the Significance of Olive Phytochemicals in Plant Physiology and Human Health

by Irene Gouvinhas^1,*

, Nelson Machado¹, Carla Sobreira¹, Raúl Domínguez-Perles¹, Sónia Gomes^2,3

, Eduardo Rosa¹ and Ana I. R. N. A. Barros¹

¹ Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, University of Trás-os-Montes and Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal

² University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal

³ BioISI–Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, Campo Grande, Lisboa, Portugal

Molecules 2017, 22(11), 1986; https://doi.org/10.3390/molecules22111986 - 16 Nov 2017

Cited by 69 | Viewed by 10366

Abstract

Olive oil displays remarkable organoleptic and nutritional features, which turn it into a foodstuff appreciated by consumers, and a basic component of the Mediterranean diet. Indeed, the noticed benefits of including olive oil in the diet have been assigned to the presence of [...] Read more.

Olive oil displays remarkable organoleptic and nutritional features, which turn it into a foodstuff appreciated by consumers, and a basic component of the Mediterranean diet. Indeed, the noticed benefits of including olive oil in the diet have been assigned to the presence of diverse bioactive compounds with different molecular structures. These compounds confer a wide range of biological properties to this food matrix, including the prevention of distinct human diseases as well as the modulation of their severity. The most relevant bioactive compounds present in olive oil correspond to benzoic and cinnamic acids, phenolic alcohols and secoiridoids, and also flavonoids. Over the last decades, several studies, devoted to gaining a further insight into the relative contribution of the separate groups and individual compounds for their biological activities, have been conducted, providing relevant information on structure–activity relationships. Therefore, this paper critically reviews the health benefits evidenced by distinct phenolic compounds found in olive oils, thus contributing to clarify the relationship between their chemical structures and biological functions, further supporting their interest as essential ingredients of wholesome foods. Full article

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

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19 pages, 3278 KiB

Open AccessFeature PaperArticle

Synthesis, Characterization and Biological Activities of Biopolymeric Schiff Bases Prepared with Chitosan and Salicylaldehydes and Their Pd(II) and Pt(II) Complexes

by Hellen Franciane Gonçalves Barbosa¹, Maha Attjioui²

, Ana Paula Garcia Ferreira¹, Edward Ralph Dockal³, Nour Eddine El Gueddari², Bruno M. Moerschbacher^2,* and Éder Tadeu Gomes Cavalheiro^2,*

¹ Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, 400, São Carlos 13566-590, SP, Brazil

² Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossplatz 8, 48143 Münster, Germany

³ Departmento de Química, Universidade Federal de São Carlos, Via Washington Luis, Km 235, São Carlos 13560-900, SP, Brazil

Molecules 2017, 22(11), 1987; https://doi.org/10.3390/molecules22111987 - 16 Nov 2017

Cited by 50 | Viewed by 8702

Abstract

In an attempt to enhance chitosan biological activities, biopolymeric Schiff bases of chitosan and different salicylaldehydes and their palladium(II) and platinum(II) complexes were synthesized and tested. The chemical structures of these derivatives were characterized using ¹H-NMR, FTIR spectroscopy and XPRD. Thermal analysis [...] Read more.

In an attempt to enhance chitosan biological activities, biopolymeric Schiff bases of chitosan and different salicylaldehydes and their palladium(II) and platinum(II) complexes were synthesized and tested. The chemical structures of these derivatives were characterized using ¹H-NMR, FTIR spectroscopy and XPRD. Thermal analysis was done through TGA/DTG-DTA. Electronic absorption spectra and surface morphologies were analyzed by SEM-EDAX. Chitosan and its derivatives were evaluated for their in vitro antimicrobial activity against two common bacterial and fungal plant pathogens Pseudomonas syringae pv. tomato and Fusarium graminearum, respectively, and for their antitumor activity against a human breast cancer cell line (MCF-7). It was found that, compared to the nonmodified chitosan, chitosan modified with Schiff bases and their complexes was highly toxic against the MCF-7 cell line and had antibacterial effects against P. syringea. However, the modified chitosan derivatives had less pronounced antifungal effects against F. graminearum compared to the nonmodified chitosan, suggesting different modes of action. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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12 pages, 809 KiB

Open AccessArticle

Lipid Peroxidation Process in Meat and Meat Products: A Comparison Study of Malondialdehyde Determination between Modified 2-Thiobarbituric Acid Spectrophotometric Method and Reverse-Phase High-Performance Liquid Chromatography

by Anna Reitznerová¹, Monika Šuleková^2,*, Jozef Nagy¹, Slavomír Marcinčák¹, Boris Semjon^1,*, Milan Čertík³ and Tatiana Klempová³

¹ Department of Food Hygiene and Technology, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia

² Department of Chemistry, Biochemistry and Biophysics, University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovakia

³ Institute of Biotechnology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, 811 07 Bratislava, Slovakia

Molecules 2017, 22(11), 1988; https://doi.org/10.3390/molecules22111988 - 16 Nov 2017

Cited by 137 | Viewed by 10738

Abstract

The aim of this work was to compare the methods of malondialdehyde detection, as the main secondary product of the lipid peroxidation process, in meat and meat products. Malondialdehyde measurements were performed by two modified methods, the 2-thiobarbituric acid spectrophotometric method and the [...] Read more.

The aim of this work was to compare the methods of malondialdehyde detection, as the main secondary product of the lipid peroxidation process, in meat and meat products. Malondialdehyde measurements were performed by two modified methods, the 2-thiobarbituric acid spectrophotometric method and the reverse-phase high-performance liquid chromatography in raw, mechanically-deboned chicken meat and in manufactured frankfurters. The malondialdehyde concentrations measured by the 2-thiobarbituric acid spectrophotometric method were found to be overestimated by more than 25% in raw meat and more than 27% in frankfurters in comparison to the results of reverse-phase high-performance liquid chromatography (p < 0.05). The achieved results showed that the presented modified reverse-phase high-performance liquid chromatography method was more applicable and more accurate for the quantification of malondialdehyde in samples of meat and meat products. Full article

(This article belongs to the Special Issue Selected Papers from the 46th EuroCongress on Drug Synthesis and Analysis (ECDSA-2017))

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18 pages, 3345 KiB

Open AccessArticle

Different Inhibitory Potencies of Oseltamivir Carboxylate, Zanamivir, and Several Tannins on Bacterial and Viral Neuraminidases as Assessed in a Cell-Free Fluorescence-Based Enzyme Inhibition Assay

by Stefanie Quosdorf¹, Anja Schuetz^2,† and Herbert Kolodziej^1,*,†

¹ Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany

² Max-Delbrück-Centrum for Molecular Medicine, Helmholtz Protein Sample Production Facility, Robert-Rössle-Str. 10, 13125 Berlin, Germany

^† These authors share last authorship.

Molecules 2017, 22(11), 1989; https://doi.org/10.3390/molecules22111989 - 17 Nov 2017

Cited by 29 | Viewed by 7829

Abstract

Neuraminidase is a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying [...] Read more.

Neuraminidase is a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA)-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1) and bacterial Vibrio cholerae neuraminidase (VCNA). Compared to the positive controls, all tested polyphenols displayed a weak inhibition of the viral enzyme but similar or even higher potency on the bacterial neuraminidase. Structure–activity relationship analyses revealed the presence of galloyl groups and the hydroxylation pattern of the flavan skeleton to be crucial for inhibitory activity. The combination of zanamivir and EPs^® 7630 (root extract of Pelargonium sidoides) showed synergistic inhibitory effects on the bacterial neuraminidase. Co-crystal structures of VCNA with oseltamivir carboxylate and zanamivir provided insight into bacterial versus viral enzyme-inhibitor interactions. The current data clearly indicate that inhibitor potency strongly depends on the biological origin of the enzyme and that results are not readily transferable. The therapeutic relevance of our findings is briefly discussed. Full article

(This article belongs to the Special Issue Special Issue Dedicated to Late Professor Takuo Okuda, “Tannins and Related Polyphenols Revisited: Chemistry, Biochemistry and Biological Activities”)

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14 pages, 1647 KiB

Open AccessArticle

Baccharis reticularia DC. and Limonene Nanoemulsions: Promising Larvicidal Agents for Aedes aegypti (Diptera: Culicidae) Control

by Gisele Da S. Botas¹

, Rodrigo A. S. Cruz²

, Fernanda B. De Almeida², Jonatas L. Duarte²

, Raquel S. Araújo², Raimundo Nonato P. Souto², Ricardo Ferreira², José Carlos T. Carvalho², Marcelo G. Santos³, Leandro Rocha⁴, Vera Lúcia P. Pereira¹ and Caio P. Fernandes^2,*

¹ Walter Mors Institute of Research on Natural Products, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil

² Department of Biological and Health Sciences, Federal University of Amapá, Macapá 68.903-419, Brazil

³ Faculty of Teacher Training, University of the State of Rio de Janeiro, São Gonçalo 24435-005, Brazil

⁴ Department of Pharmaceutical Technology, Faculty of Pharmacy, Fluminense Federal University, Niterói 24210-346, Brazil

Molecules 2017, 22(11), 1990; https://doi.org/10.3390/molecules22111990 - 17 Nov 2017

Cited by 72 | Viewed by 6894

Abstract

Baccharis reticularia DC. is a plant species from the Asteraceae family that is endemic to Brazil. Despite the great importance of Baccharis genus, no study has been carried out regarding either the phytochemical composition of B. reticularia or the evaluation of its larvicidal [...] Read more.

Baccharis reticularia DC. is a plant species from the Asteraceae family that is endemic to Brazil. Despite the great importance of Baccharis genus, no study has been carried out regarding either the phytochemical composition of B. reticularia or the evaluation of its larvicidal potential. Considering the intrinsic immiscibility of essential oils, this study shows larvicidal nanoemulsions containing the B. reticularia phytochemically characterized essential oil and its main constituent against Aedes aegypti. The major compound found was d-limonene (25.7%). The essential oil inhibited the acetylcholinesterase, one of the main targets of insecticides. The required hydrophile-lipophile balance of both nanoemulsions was 15.0. The mean droplet sizes were around 90.0 nm, and no major alterations were observed after 24 h of preparation for both formulations. After 48 h of treatment, the estimated LC₅₀ values were 118.94 μg mL⁻¹ and 81.19 μg mL⁻¹ for B. reticularia essential oil and d-limonene nanoemulsions, respectively. Morphological alterations evidenced by scanning electron micrography were observed on the larvae treated with the d-limonene nanoemulsion. This paper demonstrated a simple and ecofriendly method for obtaining B. reticularia essential oil and d-limonene aqueous nanoemulsions by a non-heating and solvent-free method, as promising alternatives for Aedes aegypti control. Full article

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

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12 pages, 11259 KiB

Open AccessArticle

DNA G-Wire Formation Using an Artificial Peptide is Controlled by Protease Activity

by Kenji Usui^1,*

, Arisa Okada¹, Shungo Sakashita¹, Masayuki Shimooka¹, Takaaki Tsuruoka¹

, Shu-ichi Nakano¹

, Daisuke Miyoshi¹, Tsukasa Mashima^2,3, Masato Katahira^2,3 and Yoshio Hamada¹

¹ Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan

² Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan

³ Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan

Molecules 2017, 22(11), 1991; https://doi.org/10.3390/molecules22111991 - 16 Nov 2017

Cited by 17 | Viewed by 6706

Abstract

The development of a switching system for guanine nanowire (G-wire) formation by external signals is important for nanobiotechnological applications. Here, we demonstrate a DNA nanostructural switch (G-wire <--> particles) using a designed peptide and a protease. The peptide consists of a PNA sequence [...] Read more.

The development of a switching system for guanine nanowire (G-wire) formation by external signals is important for nanobiotechnological applications. Here, we demonstrate a DNA nanostructural switch (G-wire <--> particles) using a designed peptide and a protease. The peptide consists of a PNA sequence for inducing DNA to form DNA–PNA hybrid G-quadruplex structures, and a protease substrate sequence acting as a switching module that is dependent on the activity of a particular protease. Micro-scale analyses via TEM and AFM showed that G-rich DNA alone forms G-wires in the presence of Ca²⁺, and that the peptide disrupted this formation, resulting in the formation of particles. The addition of the protease and digestion of the peptide regenerated the G-wires. Macro-scale analyses by DLS, zeta potential, CD, and gel filtration were in agreement with the microscopic observations. These results imply that the secondary structure change (DNA G-quadruplex <--> DNA/PNA hybrid structure) induces a change in the well-formed nanostructure (G-wire <--> particles). Our findings demonstrate a control system for forming DNA G-wire structures dependent on protease activity using designed peptides. Such systems hold promise for regulating the formation of nanowire for various applications, including electronic circuits for use in nanobiotechnologies. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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12 pages, 4584 KiB

Open AccessArticle

A New UPLC-MS/MS Method for the Characterization and Discrimination of Polysaccharides from Genus Ephedra Based on Enzymatic Digestions

by Yong-Gang Xia, Tian-Long Wang, Li-Ming Sun, Jun Liang, Bing-You Yang and Hai-Xue Kuang^*

Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China

Molecules 2017, 22(11), 1992; https://doi.org/10.3390/molecules22111992 - 17 Nov 2017

Cited by 11 | Viewed by 5171

Abstract

Ephedra sinica polysaccharides have been reported to possess important activities, so quality evaluation of polysaccharides from the genus Ephedra is urgent. In this study, enzymatic digestions were performed to establish multiple saccharide fingerprints by ultra-performance liquid chromatography with electrospray ionization triple quadrupole linear [...] Read more.

Ephedra sinica polysaccharides have been reported to possess important activities, so quality evaluation of polysaccharides from the genus Ephedra is urgent. In this study, enzymatic digestions were performed to establish multiple saccharide fingerprints by ultra-performance liquid chromatography with electrospray ionization triple quadrupole linear ion trap mass spectrometry (UPLC-ESI-TQ-MS/MS) based on a multiple-reaction monitoring in negative mode. Under optimum UPLC-ESI^--TQ-MS/MS conditions, excellent separation and quantification of 21 constituents were achieved within 20 min on a solid core column with a 1.6 μm particle using pre-column derivatization with a PMP reagent. This method, coupled with enzymatic digestions and principal component analysis, has been successfully applied to characterize and discriminate Ephedra polysaccharides attributed to different species and plant parts. The results suggest that the proposed analytical strategy could achieve a quality evaluation of plant polysaccharides from traditional Chinese medicines. Full article

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14 pages, 2086 KiB

Open AccessArticle

Polyphenolics from Albizia harveyi Exhibit Antioxidant Activities and Counteract Oxidative Damage and Ultra-Structural Changes of Cryopreserved Bull Semen

by Mansour Sobeh^1,*

, Soha A. Hassan², Mohamed A. El Raey³

, Wael A. Khalil⁴, Mahmoud A. E. Hassan⁵

and Michael Wink^1,*

¹ Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

² Department of Basic Sciences, Faculty of Dentistry, October 6 University, Cairo 12566, Egypt

³ Department of Phytochemistry and Plant Systematics, National Research Center, Dokki, Cairo 12622, Egypt

⁴ Department of Animal Production, Faculty of Agriculture, Mansoura University, Mansoura 35516, Egypt

⁵ Animal Production Research Institute, Dokki, Giza 12619, Egypt

Molecules 2017, 22(11), 1993; https://doi.org/10.3390/molecules22111993 - 17 Nov 2017

Cited by 43 | Viewed by 5201

Abstract

Albizia harveyi is a tropical deciduous tree, found across South and Eastern Africa and widely used in traditional medicine. The leaf extract ameliorated the damaging effects of the frozen-thawing process in cryopreserved bull semen. In a dose-dependent pattern, sperm motility, viability, and membrane [...] Read more.

Albizia harveyi is a tropical deciduous tree, found across South and Eastern Africa and widely used in traditional medicine. The leaf extract ameliorated the damaging effects of the frozen-thawing process in cryopreserved bull semen. In a dose-dependent pattern, sperm motility, viability, and membrane integrity were improved compared to the untreated control. Furthermore, the extract increased the percentage of viable sperm cells and reduced the percentages of early apoptotic and apoptotic sperm cells as well as the damage in sperm ultra-structure. These activities are in agreement with the robust antioxidant properties in vitro and in the seminal fluid as observed in the total antioxidant capacity and the lipid peroxidation parameter malondialdehyde. LC-MS yielded 35 compounds. The extract was dominated by quercetin-O-galloyl-hexoside and quercetin-O-pentoside, along with other flavonoid glycosides. The polyphenols are probably responsible for the observed activities. In conclusion, the current findings show that A. harveyi leaves are rich in bioactive polyphenols with functional properties, validating its traditional use. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 610 KiB

Open AccessArticle

Influence of Shenxiong Glucose Injection on the Activities of Six CYP Isozymes and Metabolism of Warfarin in Rats Assessed Using Probe Cocktail and Pharmacokinetic Approaches

by Jia Sun^1,2,3,†, Yuan Lu^1,2,†, Yueting Li^1,2, Jie Pan^1,2, Chunhua Liu^1,2

, Zipeng Gong^1,2, Jing Huang², Jiang Zheng^1,2, Lin Zheng^1,2, Yongjun Li^2,4

, Ting Liu^1,2,* and Yonglin Wang^1,2,*

¹ Key Laboratory of Pharmaceutics of Guizhou Provincial, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China

² School of Pharmacy, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China

³ National Engineering Research Center of Miao’s Medicines, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China

⁴ Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1994; https://doi.org/10.3390/molecules22111994 - 20 Nov 2017

Cited by 22 | Viewed by 4681

Abstract

Shenxiong glucose injection (SGI), a traditional Chinese medicine (TCM) preparation, has been widely used for the treatment of various cardiovascular and cerebrovascular diseases for many years. We assessed the potential influences of SGI on the activities of six CYP enzymes (CYP1A2, CYP2C11, CYP2C19, [...] Read more.

Shenxiong glucose injection (SGI), a traditional Chinese medicine (TCM) preparation, has been widely used for the treatment of various cardiovascular and cerebrovascular diseases for many years. We assessed the potential influences of SGI on the activities of six CYP enzymes (CYP1A2, CYP2C11, CYP2C19, CYP2D4, CYP2E1, and CYP3A2) and on the pharmacokinetics of warfarin in rats. We compared plasma pharmacokinetics of six probe drugs (caffeine/CYP1A2, tolbutamide/CYP2C11, omeprazole/CYP2C19, metoprolol/CYP2D4, chlorzoxazone/CYP2E1, and midazolam/CYP3A2) and of warfarin between control and SGI-pretreated groups, to estimate the effect on the relative activities of the six isozymes and warfarin metabolism. There were no significant differences in the pharmacokinetic parameters of caffeine, omeprazole, metoprolol, chlorzoxazone, and midazolam between the SGI-pretreated and control groups. However, many pharmacokinetic parameters of tolbutamide in SGI-pretreated rats were affected significantly (p < 0.05), and indicated tolbutamide metabolism in the former group was markedly slower. Moreover, SGI reduced the clearance of warfarin. These results suggested SGI showed no effects on the enzyme activities of rat CYP1A2, CYP2C19, CYP2D4, CYP2E1, and CYP3A2, but inhibited the enzyme activity of CYP2C11, and improved the blood concentration of warfarin. This suggests that the dose of warfarin may need be adjusted when co-administrated with SGI. Full article

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8 pages, 585 KiB

Open AccessArticle

Four New Glycosides from the Rhizoma of Anemarrhena asphodeloides

by Bing-You Yang^1,†, Xue-Yan Bi^2,†, Yan Liu¹, Guo-Yu Li³, Xin Yin¹ and Hai-Xue Kuang^1,*

¹ Key Laboratory of Chinese Materia Medica, Ministry of Education of Heilongjiang University of Chinese Medicine, Harbin 150040, China

² Heilongjiang Institute for Food and Drug Control, Harbin 150001, China

³ College of Pharmacy, Harbin University of Commerce, Harbin 150001, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1995; https://doi.org/10.3390/molecules22111995 - 22 Nov 2017

Cited by 6 | Viewed by 3923

Abstract

Four new compounds, aneglycoside A–C (1–3) and timosaponin U (4), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were determined through extensive spectroscopic analysis, chemical characteristics, and high-resolution mass spectrometry (HRMS). All the isolations [...] Read more.

Four new compounds, aneglycoside A–C (1–3) and timosaponin U (4), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were determined through extensive spectroscopic analysis, chemical characteristics, and high-resolution mass spectrometry (HRMS). All the isolations were evaluated for cytotoxicity against HepG2, Hela, and SGC7901 human cancer lines. Compounds 1, 2, and 4 showed weak antiproliferative activities on HepG2, Hela, and SGC7901 cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 3265 KiB

Open AccessArticle

Adding an Artificial Tail—Anchor to a Peptide-Based HIV-1 Fusion Inhibitor for Improvement of Its Potency and Resistance Profile

by Shan Su¹, Zhenxuan Ma¹, Chen Hua¹, Weihua Li², Lu Lu^1,* and Shibo Jiang^1,2,3,*

¹ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences & Shanghai Public Health Clinical Center, Fudan University, 130 Dong An Rd., Xuhui District, Shanghai 200032, China

² Key Laboratory of Reproduction Regulation of National Population and Family Planning Commission, The Shanghai Institute of Planned Parenthood Research, Institute of Reproduction and Development, Fudan University, Shanghai 200032, China

³ Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA

Molecules 2017, 22(11), 1996; https://doi.org/10.3390/molecules22111996 - 20 Nov 2017

Cited by 16 | Viewed by 5128

Abstract

Peptides derived from the C-terminal heptad repeat (CHR) of human immunodeficiency virus type 1 (HIV-1) envelope protein transmembrane subunit gp41, such as T20 (enfuvirtide), can bind to the N-terminal heptad repeat (NHR) of gp41 and block six-helix bundle (6-HB) formation, thus inhibiting HIV-1 [...] Read more.

Peptides derived from the C-terminal heptad repeat (CHR) of human immunodeficiency virus type 1 (HIV-1) envelope protein transmembrane subunit gp41, such as T20 (enfuvirtide), can bind to the N-terminal heptad repeat (NHR) of gp41 and block six-helix bundle (6-HB) formation, thus inhibiting HIV-1 fusion with the target cell. However, clinical application of T20 is limited because of its low potency and genetic barrier to resistance. HP23, the shortest CHR peptide, exhibits better anti-HIV-1 activity than T20, but the HIV-1 strains with E49K mutations in gp41 will become resistant to it. Here, we modified HP23 by extending its C-terminal sequence using six amino acid residues (E6) and adding IDL (Ile-Asp-Leu) to the C-terminus of E6, which is expected to bind to the shallow pocket in the gp41 NHR N-terminal region. The newly designed peptide, designated HP23-E6-IDL, was about 2- to 16-fold more potent than HP23 against a broad spectrum of HIV-1 strains and more than 12-fold more effective against HIV-1 mutants resistant to HP23. These findings suggest that addition of an anchor–tail to the C-terminus of a CHR peptide will allow binding with the pocket in the gp41 NHR that may increase the peptide’s antiviral efficacy and its genetic barrier to resistance. Full article

(This article belongs to the Special Issue Peptide Therapeutics)

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19 pages, 5495 KiB

Open AccessArticle

The HMGB1/RAGE Pro-Inflammatory Axis in the Human Placenta: Modulating Effect of Low Molecular Weight Heparin

by Cristian Zenerino^1,†, Anna Maria Nuzzo^1,†

, Domenica Giuffrida¹, Marilisa Biolcati¹, Alessandra Zicari², Tullia Todros¹ and Alessandro Rolfo^1,*

¹ Department of Surgical Sciences, University of Turin, 10126 Turin, Italy

² Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 1997; https://doi.org/10.3390/molecules22111997 - 17 Nov 2017

Cited by 39 | Viewed by 6386

Abstract

We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low [...] Read more.

We evaluated whether physiological and pre-eclamptic (PE) placentae, characterized by exacerbated inflammation, presented alterations in pro-inflammatory High Mobility Group Box 1 (HMGB1) and its Receptor of Advanced Glycation End products (RAGE) expression. Moreover, we investigated, in physiological placental tissue, the ability of Low Molecular Weight Heparin (LMWH) to modify HMGB1 structural conformation thus inhibiting RAGE binding and HMGB1/RAGE axis inflammatory activity. HMGB1, RAGE, IL-6 and TNFα (HMGB1/RAGE targets) mRNA expression were assessed by Real Time PCR. HMGB1, RAGE protein levels were assessed by western blot assay. Physiological term placental explants were treated by 0.5 U LMWH for 24 or 48 h. HMGB1 and RAGE expression and association were evaluated in LMWH explants by RAGE immunoprecipitation followed by HMGB1 immunoblot. HMGB1 spatial localization was evaluated by immuofluorescent staining (IF). HMGB1 expression was increased in PE relative to physiological placentae while RAGE was unvaried. 24 h LMWH treatment significantly up-regulated HMGB1 expression but inhibited HMGB1/RAGE complex formation in physiological explants. RAGE expression decreased in treated relative to untreated explants at 48 h. IF showed HMGB1 localization in both cytoplasm and nucleus of mesenchymal and endothelial cells but not in the trophoblast. IL-6 and TNFα gene expression were significantly increased at 24 h relative to controls, while they were significantly down-regulated in 48 h vs. 24 h LMWH explants. Our data depicted a new molecular mechanism through which LMWH exerts its anti-inflammatory effect on PE placentae, underlying the importance of HMGB1/RAGE axis in PE inflammatory response. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 2684 KiB

Open AccessArticle

Neuraminidase Inhibitory Activity and Constituent Characterization of Fagopyrum dibotrys

by Xiang Zhang¹

, Yu Cao¹, Jinhua Li¹, Ailin Liu², Haibo Liu^1,* and Linfang Huang^1,*

¹ Institute of Medicinal Plant Development, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100193, China

² Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Molecules 2017, 22(11), 1998; https://doi.org/10.3390/molecules22111998 - 18 Nov 2017

Cited by 9 | Viewed by 4966

Abstract

This study aimed to identify a new biological activity of the widely distributed species Fagopyrum dibotrys. Four F. dibotrys extracts (ethyl acetate (EA), petroleum ether (P), ethanol (E), and water (W)) were explored for their anti-neuraminidase (NA) activity. A total of 32 [...] Read more.

This study aimed to identify a new biological activity of the widely distributed species Fagopyrum dibotrys. Four F. dibotrys extracts (ethyl acetate (EA), petroleum ether (P), ethanol (E), and water (W)) were explored for their anti-neuraminidase (NA) activity. A total of 32 compounds were identified using UHPLC-Q-Exactive Orbitrap HRMS in the EA extract, which had the best NA inhibitory effects. We used the docking data for supporting compounds’ anti-neuraminidase activity. Among them, five compounds including one flavonoid, three organic acids, and one glucoside were discovered for the first time in F. dibotrys. Docking studies and NA activity assay revealed the remarkable NA inhibitory activity of eight components in EA extract, especially rutin, hesperidin, procyanidin B₂, and quercitrin. Therefore, F. dibotrys could be used to develop anti-influenza drugs. Full article

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

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9 pages, 1915 KiB

Open AccessArticle

Optimization of Goat Milk with ACE Inhibitory Peptides Fermented by Lactobacillus bulgaricus LB6 Using Response Surface Methodology

by Guowei Shu¹

, Xiaoyu Shi^1,*, He Chen¹, Zhe Ji¹ and Jiangpeng Meng²

¹ School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China

² Department of Research and Development, Xi’an Baiyue Gaot Milk Corp., Ltd., Xi’an 710089, China

Molecules 2017, 22(11), 2001; https://doi.org/10.3390/molecules22112001 - 21 Nov 2017

Cited by 20 | Viewed by 4968

Abstract

In the present study, the incubation conditions of goat milk fermented by Lactobacillus bulgaricus LB6 were optimized to increase the angiotensin converting enzyme (ACE, EC 3.4.15.1) inhibitory activity by Box–Behnken design of response surface methodology. Incubation temperature, whey powder, and calcium lactate had [...] Read more.

In the present study, the incubation conditions of goat milk fermented by Lactobacillus bulgaricus LB6 were optimized to increase the angiotensin converting enzyme (ACE, EC 3.4.15.1) inhibitory activity by Box–Behnken design of response surface methodology. Incubation temperature, whey powder, and calcium lactate had significant effects on ACE inhibition rate and viable counts of LB6 during incubation. The results showed that optimal conditions of fermentation were found to be 37.05 °C, 0.8% (w/w) whey powder and 0.50% (w/w) calcium lactate. ACE inhibition rate increased significantly from 71.04 ± 0.37% to 83.31 ± 0.45% and the viable counts of Lactobacillus bulgaricus LB6 reached to 8.03 × 10⁷ cfu·mL⁻¹ under the optimal conditions, which approached the predicted values 83.25% and 8.04 × 10⁷ cfu·mL⁻¹. The optimal fermentation conditions can be a good reference for preparing ACE inhibitory peptides from goat milk. Full article

(This article belongs to the Special Issue Selected Papers from the 6th International Conference on Biotechnology and Bioengineering (6-ICBB 2017))

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12 pages, 3885 KiB

Open AccessCommunication

Preparative Separation and Purification of Four Glycosides from Gentianae radix by High-Speed Counter-Current Chromatography and Comparison of Their Anti-NO Production Effects

by Bao Chen^1,2, Yinghua Peng¹, Xinhui Wang¹, Zhiman Li¹ and Yinshi Sun^1,*

¹ Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China

² College of Chinese Material Medicine, Jilin Agricultural University, Changchun 130118, China

Molecules 2017, 22(11), 2002; https://doi.org/10.3390/molecules22112002 - 17 Nov 2017

Cited by 16 | Viewed by 4556

Abstract

Secoiridoid and iridoid glycosides are the main active components of Gentianae radix. In this work, one iridoid and three secoiridoid glycosides from Gentianae radix have been purified by high-speed counter-current chromatography in two runs using different solvent systems. Ethyl acetate–n-butanol–water [...] Read more.

Secoiridoid and iridoid glycosides are the main active components of Gentianae radix. In this work, one iridoid and three secoiridoid glycosides from Gentianae radix have been purified by high-speed counter-current chromatography in two runs using different solvent systems. Ethyl acetate–n-butanol–water (2:1:3, v/v/v) was the optimum solvent system to purify ca. 4.36 mg of loganic acid, 3.05 mg of swertiamarin, and 35.66 mg of gentiopicroside with 98.1%, 97.2% and 98.6% purities, respectively, while 31.15 mg of trifloroside with 98.9% purity was separated using hexane–ethyl acetate–methanol–water (1:3:1:3, v/v/v/v). The structures of the glycosides were identified by mass spectrometry and NMR. After separation, the anti-nitric oxide production effects of the compounds on lipopolysaccharide-induced BV-2 murine microglial cells were also evaluated. All of the compounds inhibited the production of nitric oxide in lipopolysaccharide-induced BV-2 cells with high cell viabilities in a concentration-dependent manner, which demonstrated that were able to be used as a nitric oxide inhibitor. Full article

(This article belongs to the Collection Herbal Medicine Research)

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12 pages, 2347 KiB

Open AccessArticle

¹⁹F‐NMR Diastereotopic Signals in Two N-CHF₂ Derivatives of (4S,7R)-7,8,8-Trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole

by Diana García-Pérez¹

, Concepción López^1,*

, Rosa M. Claramunt¹

, Ibon Alkorta^2,*

and José Elguero²

¹ Departamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain

² Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain

Molecules 2017, 22(11), 2003; https://doi.org/10.3390/molecules22112003 - 17 Nov 2017

Cited by 10 | Viewed by 10329

Abstract

In this paper, we report the anisochrony of the fluorine atoms of a CHF₂ group when linked to a pyrazole ring. The pyrazole is part of (4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole also known as (4S,7R)-campho[2,3-c [...] Read more.

In this paper, we report the anisochrony of the fluorine atoms of a CHF₂ group when linked to a pyrazole ring. The pyrazole is part of (4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole also known as (4S,7R)-campho[2,3-c]pyrazole, which has two stereogenic centers. Gauge-Independent Atomic Orbital (GIAO)/Becke, 3-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,f) calculated ¹⁹F chemical shifts of the minimum energy conformations satisfactorily agree with the experimental data. The energy differences between minima need to consider solvent effects (continuum model) to be satisfactorily reproduced. Full article

(This article belongs to the Special Issue Pyrazole Derivatives)

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13 pages, 1326 KiB

Open AccessArticle

Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

by Serkan Levent^1,2, Betül Kaya Çavuşoğlu¹, Begüm Nurpelin Sağlık^1,2, Derya Osmaniye^1,2, Ulviye Acar Çevik^1,2, Özlem Atlı³, Yusuf Özkay^1,2,*

and Zafer Asım Kaplancıklı¹

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

² Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

³ Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey

Molecules 2017, 22(11), 2004; https://doi.org/10.3390/molecules22112004 - 18 Nov 2017

Cited by 20 | Viewed by 4573

Abstract

In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds (6a [...] Read more.

In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds (6a–6s) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, ¹H-NMR, ¹³C-NMR and HR-MS spectral data. Compounds were tested against four Candida species by broth microdilution assay. Compounds 6e, 6k and 6r, bearing a nitro group, showed significant antifungal activity against all fungi with minimum inhibitory concentration (MIC) in the range of 0.78–3.12 µg/mL. These compounds were also screened for their in vitro cytotoxic effects by MTT assay and detected as nontoxic at their active concentrations against Candida strains. To examine the effects of these compounds on ergosterol biosynthesis, the LC-MS-MS method, which is based on quantification of ergosterol level in C. krusei, was carried out. Finally, the most active molecule (6e) was docked in the active site of the lanosterol 14α-demethylase enzyme, and it was determined that there is a strong interaction between the compound and enzyme. Full article

(This article belongs to the Special Issue Emerging Drug Discovery Approaches against Infectious Diseases)

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13 pages, 1426 KiB

Open AccessArticle

New Tripentone Analogs with Antiproliferative Activity

by Barbara Parrino, Salviana Ullo, Alessandro Attanzio, Virginia Spanò, Stella Cascioferro

, Alessandra Montalbano, Paola Barraja, Luisa Tesoriere, Girolamo Cirrincione and Patrizia Diana^*

Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, Italy

Molecules 2017, 22(11), 2005; https://doi.org/10.3390/molecules22112005 - 18 Nov 2017

Cited by 12 | Viewed by 3667

Abstract

Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz [...] Read more.

Tripentones represent an interesting class of compounds due to their significant cytotoxicity against different human tumor cells in the submicro-nanomolar range. New tripentone analogs, in which a pyridine moiety replaces the thiophene ring originating the fused azaindole system endowed with anticancer activity viz 8H-thieno[2,3-b]pyrrolizinones, were efficiently synthesized in four steps with fair overall yields (34–57%). All tripentone derivatives were tested in the range of 0.1–100 μM for cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivative, with GI₅₀ values of 4.25 µM and 20.73 µM for HCT-116 and MCF-7 cells, respectively, did not affect the viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of its cytotoxic action. The same compound was further investigated in order to study its mode of action. Results showed that it did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis. Flow cytometric analysis demonstrated that this compound caused cell cycle alteration, inhibiting its progression in S and G2/M phases. Full article

(This article belongs to the Special Issue The Biomedical Importance of Indoles and Their Derivatives)

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11 pages, 539 KiB

Open AccessArticle

Identification of Major Flavone C-Glycosides and Their Optimized Extraction from Cymbidium kanran Using Deep Eutectic Solvents

by Kyung Min Jeong¹, Misuk Yang², Yan Jin¹, Eun Mi Kim¹, Jaeyoung Ko^2,* and Jeongmi Lee^1,*

¹ School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, Korea

² Amorepacific Research and Development Center, Giheung-gu, Yongin 17074, Gyeonggi-do, Korea

Molecules 2017, 22(11), 2006; https://doi.org/10.3390/molecules22112006 - 18 Nov 2017

Cited by 19 | Viewed by 5753

Abstract

Cymbidium kanran, an orchid exclusively distributed in Northeast Asia, has been highly valued as a decorative plant and traditional herbal medicine. Here, C. kanran extracts were prepared in 70% aqueous methanol using ultrasound-assisted extraction (UAE) and subjected to liquid chromatography-photodiode array detection [...] Read more.

Cymbidium kanran, an orchid exclusively distributed in Northeast Asia, has been highly valued as a decorative plant and traditional herbal medicine. Here, C. kanran extracts were prepared in 70% aqueous methanol using ultrasound-assisted extraction (UAE) and subjected to liquid chromatography-photodiode array detection and ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry analysis, which were used for quantitative and qualitative analysis, respectively. It was found that the extracts were rich in flavone C-glycosides including vicenin-2, vicenin-3, schaftoside, vitexin, and isovitexin. Ten deep eutectic solvents (DESs) were synthesized by combining choline chloride (hydrogen bond acceptor) with various polyols and diols (hydrogen bond donors) and were tested as a medium for the efficient production of extracts enriched with potentially bioactive flavone C-glycosides from C. kanran. A DES named ChCl:DPG, composed of choline chloride and dipropylene glycol at a 1:4 molar ratio, exhibited the best extraction yields. Then, the effects of extraction conditions on the extraction efficiency were investigated by response surface methodology. Lower water content in the extraction solvent and longer extraction time during UAE were desirable for higher extraction yields. Under the statistically optimized conditions, in which 100 mg of C. kanran powder were extracted in 0.53 mL of a mixture of ChCl:DPG and water (74:26, w/w) for 86 min, a total of 3.441 mg g⁻¹ flavone C-glycosides including 1.933 mg g⁻¹ vicenin-2 was obtained. This total yield was 196%, 131%, and 71% more than those obtained using 100% methanol, water, and 70% methanol, respectively. Full article

(This article belongs to the Special Issue Green Extraction of Natural Product: Innovative Techniques, Alternative Solvents and Original Procedures)

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28 pages, 7082 KiB

Open AccessArticle

Studies for Improving a Rat Model of Alzheimer’s Disease: Icv Administration of Well-Characterized β-Amyloid 1-42 Oligomers Induce Dysfunction in Spatial Memory

by Ágnes Kasza¹, Botond Penke^1,*, Zsuzsanna Frank¹, Zsolt Bozsó¹, Viktor Szegedi¹

, Ákos Hunya², Klaudia Németh¹, Gábor Kozma³

and Lívia Fülöp¹

¹ Department of Medical Chemistry, University of Szeged, Dome square 8, Szeged H-6720, Hungary

² LipidArt Research and Development Ltd., Temesvári krt. 62, Szeged H-6726, Hungary

³ Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla square 1, Szeged H-6720, Hungary

Molecules 2017, 22(11), 2007; https://doi.org/10.3390/molecules22112007 - 18 Nov 2017

Cited by 60 | Viewed by 10981

Abstract

During the past 15 years, several genetically altered mouse models of human Alzheimer’s disease (AD) have been developed. These costly models have greatly facilitated the evaluation of novel therapeutic approaches. Injecting synthetic β-amyloid (Aβ) 1-42 species into different parts of the brain of [...] Read more.

During the past 15 years, several genetically altered mouse models of human Alzheimer’s disease (AD) have been developed. These costly models have greatly facilitated the evaluation of novel therapeutic approaches. Injecting synthetic β-amyloid (Aβ) 1-42 species into different parts of the brain of non-transgenic rodents frequently provided unreliable results, owing to a lack of a genuine characterization of the administered Aβ aggregates. Previously, we have published a new rat AD-model in which protofibrillar-fibrillar Aβ1-42 was administered into rat entorhinal cortex (Sipos 2007). In order to develop a more reliable model, we have injected well-characterized toxic soluble Aβ1-42 species (oligomers, protofibrils and fibrils) intracerebroventricularly (icv) into rat brain. Studies of the distribution of fluorescent-labeled Aβ1-42 in the brain showed that soluble Aβ-species diffused into all parts of the rat brain. After seven days, the Aβ-treated animals showed a significant decrease of spatial memory in Morris water maze test and impairment of synaptic plasticity (LTP) measured in acute hippocampal slices. The results of histological studies (decreased number of viable neurons, increased tau levels and decreased number of dendritic spines) also supported that icv administration of well-characterized toxic soluble Aβ species into rat brain provides a reliable rat AD-model. Full article

(This article belongs to the Special Issue 25th Anniversary of the Amyloid Hypothesis and Alzheimer Disease)

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16 pages, 2096 KiB

Open AccessArticle

Biodegradable Chitosan Decreases the Immune Response to Trichinella spiralis in Mice

by Klaudia Brodaczewska¹, Natalia Wolaniuk¹, Katarzyna Lewandowska², Katarzyna Donskow-Łysoniewska¹ and Maria Doligalska^1,*

¹ Department of Parasitology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland

² Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 87-100 Toruń, Poland

Molecules 2017, 22(11), 2008; https://doi.org/10.3390/molecules22112008 - 18 Nov 2017

Cited by 16 | Viewed by 5987

Abstract

The purpose of this study was to evaluate the potential of chitosan units released during natural degradation of the polymer to activate the immune system against T. spiralis infection. High molecular weight chitosan was injected intraperitoneally into C57BL/6 mice. Flow cytometry and cytokine [...] Read more.

The purpose of this study was to evaluate the potential of chitosan units released during natural degradation of the polymer to activate the immune system against T. spiralis infection. High molecular weight chitosan was injected intraperitoneally into C57BL/6 mice. Flow cytometry and cytokine concentration, measured by ELISA, were used to characterize peritoneal cell populations during T. spiralis infection. The strong chemo-attractive properties of chitosan caused considerable infiltration into the peritoneal cavity of CD11b⁺ cells, with reduced expression of MHC class II, CD80, CD86, Dectin-1 or CD23 receptors in comparison to T. spiralis-infected mice. After prolonged chitosan biodegradation, cell populations expressing IL-4R, MR and Dectin-1 receptors were found to coexist with elevated IL-6, IL-10, TGF-β and IgA production. IgA cross-reacted with T. spiralis antigen and chitosan. It was found that chitosan treatment attracted immune cells with low activity, which resulted in the number of nematodes increasing. The glucosamine and N-acetyl-D-glucosamine residues were recognized by wheat germ agglutinin (WGA) lectin and therefore any biodegradable chitosan units may actively downregulate the immune response to the parasite. The findings are relevant for both people and animals treated with chitosan preparations. Full article

(This article belongs to the Special Issue Chitin and Chitosan Derivatives: Biological Activities and Application)

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10 pages, 2095 KiB

Open AccessFeature PaperArticle

Enhancement of Aggregation-Induced Emission by Introducing Multiple o-Carborane Substitutions into Triphenylamine

by Kenta Nishino, Kyoya Uemura, Masayuki Gon, Kazuo Tanaka^* and Yoshiki Chujo^*

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan

Molecules 2017, 22(11), 2009; https://doi.org/10.3390/molecules22112009 - 19 Nov 2017

Cited by 42 | Viewed by 6476

Abstract

The enhancement of aggregation-induced emission (AIE) is presented on the basis of the strategy for improving solid-state luminescence by employing multiple o-carborane substituents. We synthesized the modified triphenylamines with various numbers of o-carborane units and compared their optical properties. From the [...] Read more.

The enhancement of aggregation-induced emission (AIE) is presented on the basis of the strategy for improving solid-state luminescence by employing multiple o-carborane substituents. We synthesized the modified triphenylamines with various numbers of o-carborane units and compared their optical properties. From the optical measurements, the emission bands from the twisted intramolecular charge transfer (TICT) state were obtained from the modified triphenylamines. It was notable that emission efficiencies of the multi-substituted triphenylamines including two or three o-carborane units were enhanced 6- to 8-fold compared to those of the mono-substituted triphenylamine. According to mechanistic studies, it was proposed that the single o-carborane substitution can load the AIE property via the TICT mechanism. It was revealed that the additional o-carborane units contribute to improving solid-state emission by suppressing aggregation-caused quenching (ACQ). Subsequently, intense AIEs were obtained. This paper presents a new role of the o-carborane substituent in the enhancement of AIEs. Full article

(This article belongs to the Special Issue Aggregation-Induced Emission: Commemorative Issue in Honor of Professor Ben Zhong Tang’s Research Achievements on the Occasion of His 60th Birthday)

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20 pages, 2070 KiB

Open AccessArticle

Synthesis and Improved Cross-Linking Properties of C5-Modified Furan Bearing PNAs

by Joke Elskens^1,†, Alex Manicardi^1,2,†

, Valentina Costi², Annemieke Madder^1,*

and Roberto Corradini^2,*

¹ Organic and Biomimetic Chemistry Research Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent, Belgium

² Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy

^† These authors contributed equally to the work.

Molecules 2017, 22(11), 2010; https://doi.org/10.3390/molecules22112010 - 20 Nov 2017

Cited by 17 | Viewed by 7273

Abstract

Over the past decades, peptide nucleic acid/DNA (PNA:DNA) duplex stability has been improved via backbone modification, often achieved via introducing an amino acid side chain at the α- or γ-position in the PNA sequence. It was previously shown that interstrand cross-linking can further [...] Read more.

Over the past decades, peptide nucleic acid/DNA (PNA:DNA) duplex stability has been improved via backbone modification, often achieved via introducing an amino acid side chain at the α- or γ-position in the PNA sequence. It was previously shown that interstrand cross-linking can further enhance the binding event. In this work, we combined both strategies to fine-tune PNA crosslinking towards single stranded DNA sequences using a furan oxidation-based crosslinking method; for this purpose, γ-l-lysine and γ-l-arginine furan-PNA monomers were synthesized and incorporated in PNA sequences via solid phase synthesis. It was shown that the l-lysine γ-modification had a beneficial effect on crosslink efficiency due to pre-organization of the PNA helix and a favorable electrostatic interaction between the positively-charged lysine and the negatively-charged DNA backbone. Moreover, the crosslink yield could be optimized by carefully choosing the type of furan PNA monomer. This work is the first to describe a selective and biocompatible furan crosslinking strategy for crosslinking of γ-modified PNA sequences towards single-stranded DNA. Full article

(This article belongs to the Special Issue Molecular Properties and the Applications of Peptide Nucleic Acids)

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21 pages, 4886 KiB

Open AccessArticle

Comparison of the Chemical Profiles and Antioxidant Activities of Different Parts of Cultivated Cistanche deserticola Using Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry and a 1,1-Diphenyl-2-picrylhydrazyl-Based Assay

by Xiaoming Wang¹, Jinfang Wang¹, Huanyu Guan¹, Rong Xu¹, Xiaomei Luo¹, Meifeng Su², Xiaoyan Chang¹, Wenting Tan², Jun Chen¹ and Yue Shi^1,*

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100193, China

² Beijing University of Chinese Medicine, Beijing 100102, China

Molecules 2017, 22(11), 2011; https://doi.org/10.3390/molecules22112011 - 20 Nov 2017

Cited by 29 | Viewed by 5735

Abstract

In this study, a sensitive ultra-performance liquid chromatography-photodiode array coupled to quadruple time-of-flight mass (UPLC-PDA-Q/TOF-MS) method and a 1,1-diphenyl-2- picrylhydrazyl (DPPH)-based assay were used to determine the chemical constituents and screen the antioxidant activity profiles of the methanol extracts of different parts of [...] Read more.

In this study, a sensitive ultra-performance liquid chromatography-photodiode array coupled to quadruple time-of-flight mass (UPLC-PDA-Q/TOF-MS) method and a 1,1-diphenyl-2- picrylhydrazyl (DPPH)-based assay were used to determine the chemical constituents and screen the antioxidant activity profiles of the methanol extracts of different parts of cultivated Cistanche deserticola (C. deserticola). First, qualitative and quantitative chemical composition analyses of the different parts of cultivated C. deserticola were conducted. Obvious differences were observed between the chemical profiles and content distribution of phenylethanoid glycosides (PhGs) from the different cultivated C. deserticola parts. The average contents of the six PhGs parts varied from 4.91 to 72.56 mg/g DW (milligrams of extract per gram of plant dry weight) in the six different parts of Cistanche deserticola, displaying a significant decreasing trend from the bottom to the top of cultivated C. deserticola and the highest content in the stems. From the bottom to the top of the plant, the echinacoside and cistanoside A content decreased and the 2

^{'}

-acetylacteoside content increased. Second, an offline DPPH assay revealed that the total scavenging activities of all parts within the range of 20–500

μ

g/mL increased in a concentration-dependent manner and that good antioxidant activities were found in all plant parts, particularly in the stems, which could be related to their higher PhG content. Additionally, a DPPH-UPLC-PDA method was successfully applied to rapidly screen the antioxidant profiles and antioxidant components of the different cultivated C. deserticola parts. According to the antioxidant profiles before and after the DPPH reaction, there were wide variations in the antioxidant activities of different cultivated C. deserticola parts. Moreover, the antioxidant profiles revealed the presence of major free radical scavengers identified as PhGs using UPLC-Q/TOF-MS. Finally, the established DPPH-UPLC-PDA method was reagent saving, rapid and feasible for correlating the chemical profile of traditional chinese medicines (TCMs) with their bioactivities without isolation and purification and may be used for multicomponent analysis of active substances in other foods and herbs. Therefore, to better harness C. deserticola resources, using this method to evaluate cultivated C. deserticola, a promising herb material with obvious antioxidant activity, is crucial. Full article

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16 pages, 6754 KiB

Open AccessArticle

The Complete Chloroplast Genome Sequences of Aconitum pseudolaeve and Aconitum longecassidatum, and Development of Molecular Markers for Distinguishing Species in the Aconitum Subgenus Lycoctonum

by Inkyu Park, Sungyu Yang, Goya Choi, Wook Jin Kim and Byeong Cheol Moon^*

K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, Korea

Molecules 2017, 22(11), 2012; https://doi.org/10.3390/molecules22112012 - 21 Nov 2017

Cited by 53 | Viewed by 5505

Abstract

Aconitum pseudolaeve Nakai and Aconitum longecassidatum Nakai, which belong to the Aconitum subgenus Lycoctonum, are distributed in East Asia and Korea. Aconitum species are used in herbal medicine and contain highly toxic components, including aconitine. A. pseudolaeve, an endemic species of [...] Read more.

Aconitum pseudolaeve Nakai and Aconitum longecassidatum Nakai, which belong to the Aconitum subgenus Lycoctonum, are distributed in East Asia and Korea. Aconitum species are used in herbal medicine and contain highly toxic components, including aconitine. A. pseudolaeve, an endemic species of Korea, is a commercially valuable material that has been used in the manufacture of cosmetics and perfumes. Although Aconitum species are important plant resources, they have not been extensively studied, and genomic information is limited. Within the subgenus Lycoctonum, which includes A. pseudolaeve and A. longecassidatum, a complete chloroplast (CP) genome is available for only one species, Aconitum barbatum Patrin ex Pers. Therefore, we sequenced the complete CP genomes of two Aconitum species, A. pseudolaeve and A. longecassidatum, which are 155,628 and 155,524 bp in length, respectively. Both genomes have a quadripartite structure consisting of a pair of inverted repeated regions (51,854 and 52,108 bp, respectively) separated by large single-copy (86,683 and 86,466 bp) and small single-copy (17,091 and 16,950 bp) regions similar to those in other Aconitum CP genomes. Both CP genomes consist of 112 unique genes, 78 protein-coding genes, 4 ribosomal RNA (rRNA) genes, and 30 transfer RNA (tRNA) genes. We identified 268 and 277 simple sequence repeats (SSRs) in A. pseudolaeve and A. longecassidatum, respectively. We also identified potential 36 species-specific SSRs, 53 indels, and 62 single-nucleotide polymorphisms (SNPs) between the two CP genomes. Furthermore, a comparison of the three Aconitum CP genomes from the subgenus Lycoctonum revealed highly divergent regions, including trnK-trnQ, ycf1-ndhF, and ycf4-cemA. Based on this finding, we developed indel markers using indel sequences in trnK-trnQ and ycf1-ndhF. A. pseudolaeve, A. longecassidatum, and A. barbatum could be clearly distinguished using the novel indel markers AcoTT (Aconitum trnK-trnQ) and AcoYN (Aconitum ycf1-ndhF). These two new complete CP genomes provide useful genomic information for species identification and evolutionary studies of the Aconitum subgenus Lycoctonum. Full article

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11 pages, 13651 KiB

Open AccessArticle

Anti-Bacterial and Microecosystem-Regulating Effects of Dental Implant Coated with Dimethylaminododecyl Methacrylate

by Bolei Li^1,2,3, Yang Ge^1,2,3, Yao Wu⁴, Jing Chen^1,2,3, Hockin H. K. Xu⁵, Minggang Yang⁴, Mingyun Li^1,2, Biao Ren^1,2, Mingye Feng^1,2, Michael D. Weir⁵, Xian Peng^1,2,*, Lei Cheng^1,2,3,* and Xuedong Zhou^1,2,3,*

¹ State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China

² National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu 610041, China

³ Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, China

⁴ National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China

⁵ Department of Advanced Oral Sciences & Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA

Molecules 2017, 22(11), 2013; https://doi.org/10.3390/molecules22112013 - 20 Nov 2017

Cited by 25 | Viewed by 5608

Abstract

The effects of dimethylaminododecyl methacrylate (DMADDM) modified titanium implants on bacterial activity and microbial ecosystem of saliva-derived biofilm were investigated for the first time. Titanium discs were coated with DMADDM solutions at mass fractions of 0 mg/mL (control), 1, 5 and 10 mg/mL, [...] Read more.

The effects of dimethylaminododecyl methacrylate (DMADDM) modified titanium implants on bacterial activity and microbial ecosystem of saliva-derived biofilm were investigated for the first time. Titanium discs were coated with DMADDM solutions at mass fractions of 0 mg/mL (control), 1, 5 and 10 mg/mL, respectively. Biomass accumulation and metabolic activity of biofilms were tested using crystal violet assay and MTT (3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 16S rRNA gene sequencing was performed to measure the microbial community. Live/dead staining and scanning electron microscopy (SEM) were used to value the structure of biofilm. The results showed that the higher mass fraction of DMADDM the coating solution had, the significantly lower the values of metabolic activity and accumulated biofilms got, as well as fewer live cells and less extracellular matrix. Moreover, 5 mg/mL of DMADDM was the most effective concentration, as well as 10 mg/mL. In microecosystem-regulation, the DMADDM modified titanium implant decreased the relative abundance of Neisseria and Actinomyces and increased the relative abundance of Lactobacillus, a probiotic for peri-implant diseases. In conclusion, via inhibiting growth and regulating microecosystem of biofilm, this novel titanium implant coating with DMADDM was promising in preventing peri-implant disease in an ‘ecological manner’. Full article

(This article belongs to the Special Issue Antibacterial Materials and Coatings)

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19 pages, 5152 KiB

Open AccessArticle

Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

by Cristina Mihaela Ghiciuc^1,†

, Aurel Lulu Strat^1,2,†, Lacramioara Ochiuz^3,*

, Catalina Elena Lupusoru¹, Maria Ignat⁴

, Aurelia Vasile⁴, Alexandru Grigorovici⁵, Iulian Stoleriu⁶

and Carmen Solcan⁷

¹ Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania

² Laboratory of Microbiology, Hospital of Infectious Diseases “Saint Parascheva”, 2, Octav Botez Street, 700116 Iasi, Romania

³ Department of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania

⁴ Faculty of Chemistry, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700560 Iasi, Romania

⁵ Department of Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16, University Street, 700115 Iasi, Romania

⁶ Faculty of Mathematics, “Al. I. Cuza” University, 11, Blvd. Carol the 1st, 700506 Iasi, Romania

⁷ Department of Molecular Biology, Histology and Embriology, Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine “Ion Ionescu de la Brad”, 8, Mihail Sadoveanu Alley, 700489 Iasi, Romania

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 2014; https://doi.org/10.3390/molecules22112014 - 20 Nov 2017

Cited by 6 | Viewed by 4159

Abstract

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due [...] Read more.

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems). Full article

(This article belongs to the Section Medicinal Chemistry)

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23 pages, 1012 KiB

Open AccessFeature PaperReview

Taxon- and Site-Specific Melatonin Catabolism

by Rüdiger Hardeland

Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Bürgerstr 50, D-37073 Göttingen, Germany

Molecules 2017, 22(11), 2015; https://doi.org/10.3390/molecules22112015 - 21 Nov 2017

Cited by 59 | Viewed by 8549

Abstract

Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism [...] Read more.

Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism can be expected upon UV exposure, e.g., in plants and in the human skin. Additionally, melatonin is more strongly nonenzymatically degraded at sites of inflammation. Typical products are several hydroxylated derivatives of melatonin and N¹-acetyl-N²-formyl-5-methoxykynuramine (AFMK). Most of these products are also formed by enzymatic catalysis. Considerable taxon- and site-specific differences are observed in the main enzymatic routes of catabolism. Formation of 6-hydroxymelatonin by cytochrome P₄₅₀ subforms are prevailing in vertebrates, predominantly in the liver, but also in the brain. In pineal gland and non-mammalian retina, deacetylation to 5-methoxytryptamine (5-MT) plays a certain role. This pathway is quantitatively prevalent in dinoflagellates, in which 5-MT induces cyst formation and is further converted to 5-methoxyindole-3-acetic acid, an end product released to the water. In plants, the major route is catalyzed by melatonin 2-hydroxylase, whose product is tautomerized to 3-acetamidoethyl-3-hydroxy-5-methoxyindolin-2-one (AMIO), which exceeds the levels of melatonin. Formation and properties of various secondary products are discussed. Full article

(This article belongs to the Special Issue Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms)

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13 pages, 1434 KiB

Open AccessArticle

Organocatalytic Access to Enantioenriched Spirooxindole-Based 4-Methyleneazetidines

by Giulia Rainoldi¹, Matteo Faltracco², Claudia Spatti¹, Alessandra Silvani^1,*

and Giordano Lesma¹

¹ Department of Chemistry, University of Milan, via Golgi 19, 20133 Milan, Italy

² Department of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules Medicines & Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands

Molecules 2017, 22(11), 2016; https://doi.org/10.3390/molecules22112016 - 21 Nov 2017

Cited by 16 | Viewed by 4760

Abstract

This work describes the synthesis of enantioenriched spiro compounds, incorporating the azetidine and the oxindole motifs. The preparation relies on a formal [2 + 2] annulation reaction of isatin-derived N-tert-butylsulfonyl ketimines with allenoates. The asymmetric induction is secured by an [...] Read more.

This work describes the synthesis of enantioenriched spiro compounds, incorporating the azetidine and the oxindole motifs. The preparation relies on a formal [2 + 2] annulation reaction of isatin-derived N-tert-butylsulfonyl ketimines with allenoates. The asymmetric induction is secured by an organocatalytic strategy, exploiting a bifunctional cinchona-type β-isocupridine-based catalyst. Some post-transformation products, including unexpected spiropyrroline and 3,3-disubstituted oxindole derivatives, are also presented. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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13 pages, 2217 KiB

Open AccessArticle

How Secondary and Tertiary Amide Moieties are Molecular Stations for Dibenzo-24-crown-8 in [2]Rotaxane Molecular Shuttles?

by Benjamin Riss-Yaw, Justine Morin, Caroline Clavel and Frédéric Coutrot^*

Supramolecular Machines and ARchitectures Team, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS, Université Montpellier, ENSCM, Case Courrier 1706, Bâtiment Chimie (17), 3ème étage, Faculté des Sciences, Place Eugène Bataillon, 34095 Montpellier CEDEX 5, France

Molecules 2017, 22(11), 2017; https://doi.org/10.3390/molecules22112017 - 21 Nov 2017

Cited by 25 | Viewed by 6088

Abstract

Interlocked molecular machines like [2]rotaxanes are intriguing aesthetic molecules. The control of the localization of the macrocycle, which surrounds a molecular axle, along the thread leads to translational isomers of very different properties. Although many moieties have been used as sites of interactions [...] Read more.

Interlocked molecular machines like [2]rotaxanes are intriguing aesthetic molecules. The control of the localization of the macrocycle, which surrounds a molecular axle, along the thread leads to translational isomers of very different properties. Although many moieties have been used as sites of interactions for crown ethers, the very straightforwardly obtained amide motif has more rarely been envisaged as molecular station. In this article, we report the use of secondary and tertiary amide moieties as efficient secondary molecular station in pH-sensitive molecular shuttles. Depending on the N-substitution of the amide station, and on deprotonation or deprotonation-carbamoylation, the actuation of the molecular machinery differs accordingly to very distinct interactions between the axle and the DB24C8. Full article

(This article belongs to the Special Issue Interlocked Molecules, Molecular Machines, Motors and Muscles)

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22 pages, 5576 KiB

Open AccessFeature PaperReview

Synthesis of Nitrogen Heterocycles Using Samarium(II) Iodide

by Shicheng Shi

and Michal Szostak^*

Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA

Molecules 2017, 22(11), 2018; https://doi.org/10.3390/molecules22112018 - 21 Nov 2017

Cited by 27 | Viewed by 11785

Abstract

Nitrogen heterocycles represent vital structural motifs in biologically-active natural products and pharmaceuticals. As a result, the development of new, convenient and more efficient processes to N-heterocycles is of great interest to synthetic chemists. Samarium(II) iodide (SmI₂, Kagan’s reagent) has been [...] Read more.

Nitrogen heterocycles represent vital structural motifs in biologically-active natural products and pharmaceuticals. As a result, the development of new, convenient and more efficient processes to N-heterocycles is of great interest to synthetic chemists. Samarium(II) iodide (SmI₂, Kagan’s reagent) has been widely used to forge challenging C–C bonds through reductive coupling reactions. Historically, the use of SmI₂ in organic synthesis has been focused on the construction of carbocycles and oxygen-containing motifs. Recently, significant advances have taken place in the use of SmI₂ for the synthesis of nitrogen heterocycles, enabled in large part by the unique combination of high reducing power of this reagent (E_1/2 of up to −2.8 V) with excellent chemoselectivity of the reductive umpolung cyclizations mediated by SmI₂. In particular, radical cross-coupling reactions exploiting SmI₂-induced selective generation of aminoketyl radicals have emerged as concise and efficient methods for constructing 2-azabicycles, pyrrolidines and complex polycyclic barbiturates. Moreover, a broad range of novel processes involving SmI₂-promoted formation of aminyl radicals have been leveraged for the synthesis of complex nitrogen-containing molecular architectures by direct and tethered pathways. Applications to the synthesis of natural products have highlighted the generality of processes and the intermediates accessible with SmI₂. In this review, recent advances involving the synthesis of nitrogen heterocycles using SmI₂ are summarized, with a major focus on reductive coupling reactions that enable one-step construction of nitrogen-containing motifs in a highly efficient manner, while taking advantage of the spectacular selectivity of the venerable Kagan’s reagent. Full article

(This article belongs to the Section Organic Chemistry)

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11 pages, 3209 KiB

Open AccessArticle

The Protective Effects of Astaxanthin on the OVA-Induced Asthma Mice Model

by Yun-Ho Hwang¹, Seong-Gyeol Hong¹, Seul-Ki Mun¹, Su-Jin Kim¹, Sung-Ju Lee¹, Jong-Jin Kim², Kyung-Yun Kang³ and Sung-Tae Yee^1,*

¹ College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon 540-950, Korea

² Singapore Bioimaging Consortium, Agency for Science, Technology and Research, 11 Biopolis Way, No. 02-02 Helios, Singapore 138667, Singapore

³ Suncheon Research Center for Natural Medicines, Suncheon 540-950, Korea

Molecules 2017, 22(11), 2019; https://doi.org/10.3390/molecules22112019 - 21 Nov 2017

Cited by 41 | Viewed by 9498

Abstract

Although astaxanthin has a variety of biological activities such as anti-oxidant effects, inhibitory effects on skin deterioration and anti-inflammatory effects, its effect on asthma has not been studied. In this paper, the inhibitory effect of astaxanthin on airway inflammation in a mouse model [...] Read more.

Although astaxanthin has a variety of biological activities such as anti-oxidant effects, inhibitory effects on skin deterioration and anti-inflammatory effects, its effect on asthma has not been studied. In this paper, the inhibitory effect of astaxanthin on airway inflammation in a mouse model of ovalbumin (OVA)-induced asthma was investigated. We evaluated the number of total cells, Th1/2 mediated inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness as well as histological structure. The level of total IgE, IgG1, IgG2a, OVA-specific IgG1, and OVA-specific IgG2a were also examined. The oral administration of 50 mg/mL astaxanthin inhibited the respiratory system resistance, elastance, newtonian resistance, tissue damping, and tissue elastance. Also, astaxanthin suppressed the total cell number, IL-4, and IL-5, and increased the IFN-γ in the BALF. In the sera, total IgE, IgG1, and OVA-specific IgG1 were reduced by astaxanthin exposure and IgG2a and OVA-specific IgG2a were enhanced via oral administration of astaxanthin. Infiltration of inflammatory cells in the lung, production of mucus, lung fibrosis, and expression of caspase-1 or caspase-3 were suppressed in OVA-induced asthmatic animal treated with astaxanthin. These results suggest that astaxanthin may have therapeutic potential for treating asthma via inhibiting Th2-mediated cytokine and enhancing Th1-mediated cytokine. Full article

(This article belongs to the Special Issue Dietary Antioxidants: Evidence of Protective Effects against Chronic Disease)

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20 pages, 8086 KiB

Open AccessArticle

Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles—A Platform for Drug Development

by Henrika Wickström^1,2, Ellen Hilgert^1,2, Johan O. Nyman¹, Diti Desai¹, Didem Şen Karaman¹, Thomas De Beer², Niklas Sandler¹ and Jessica M. Rosenholm^1,*

¹ Pharmaceutical Sciences Laboratory, Åbo Akademi University, FI-20520 Turku, Finland

² Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, B-9000 Ghent, Belgium

Molecules 2017, 22(11), 2020; https://doi.org/10.3390/molecules22112020 - 21 Nov 2017

Cited by 53 | Viewed by 9269

Abstract

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved [...] Read more.

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN–PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials. Full article

(This article belongs to the Special Issue Mesoporous Silica in Biomedical Applications)

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10 pages, 1607 KiB

Open AccessArticle

Transformation of a Thermostable G-Quadruplex Structure into DNA Duplex Driven by Reverse Gyrase

by Dawei Li^1,*, Qiang Wang¹, Yun Liu¹, Kun Liu², Qiang Zhuge¹ and Bei Lv^2,*

¹ Key Lab of Forest Genetics and Biotechnology, Nanjing Forestry University, 159 Longpan Road, Nanjing 210037, China

² Jiangsu Key Laboratory for Biofunctional Molecules, College of Life Science and Chemistry, Jiangsu Second Normal University, Nanjing 210037, China

Molecules 2017, 22(11), 2021; https://doi.org/10.3390/molecules22112021 - 22 Nov 2017

Cited by 1 | Viewed by 6200

Abstract

Reverse gyrase is a topoisomerase that can introduce positive supercoils to its substrate DNA. It is demonstrated in our studies that a highly thermal stable G-quadruplex structure in a mini-plasmid DNA was transformed into its duplex conformation after a treatment with reverse gyrase. [...] Read more.

Reverse gyrase is a topoisomerase that can introduce positive supercoils to its substrate DNA. It is demonstrated in our studies that a highly thermal stable G-quadruplex structure in a mini-plasmid DNA was transformed into its duplex conformation after a treatment with reverse gyrase. The structural difference of the topoisomers were verified and analyzed by gel electrophoresis, atomic force microscopy examination, and endonuclease digestion assays. All evidence suggested that the overwinding structure of positive supercoil could provide a driven force to disintegrate G-quadruplex and reform duplex. The results of our studies could suggest that hyperthermophiles might use reverse gyrase to manipulate the disintegration of non-B DNA structures and safekeep their genomic information. Full article

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9 pages, 2231 KiB

Open AccessArticle

Microneedle-Assisted Percutaneous Delivery of a Tetramethylpyrazine-Loaded Microemulsion

by Qiang Zu^1,2,†, Yanyan Yu^3,†, Xiaolin Bi^1,2, Ren Zhang⁴ and Liuqing Di^1,2,*

¹ School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China

² Jiangsu Provincial TCM Engineering Technology Research Center for Highly Efficient Drug Delivery Systems (DDS), Nanjing 210023, China

³ School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China

⁴ Shanghai Hutchison Pharmaceuticals Limited, Shanghai 200001, China

^† These authors contributed equally to this work.

Molecules 2017, 22(11), 2022; https://doi.org/10.3390/molecules22112022 - 21 Nov 2017

Cited by 12 | Viewed by 4217

Abstract

This study examined the efficacy of the percutaneous delivery of a tetramethylpyrazine-loaded microemulsion (TMP-ME) on skin pretreated with microneedles (MN). The TMP-ME formulation was optimized in vitro with skin permeation experiments, using a uniform experimental design, guided by a pseudo-ternary phase diagram, in [...] Read more.

This study examined the efficacy of the percutaneous delivery of a tetramethylpyrazine-loaded microemulsion (TMP-ME) on skin pretreated with microneedles (MN). The TMP-ME formulation was optimized in vitro with skin permeation experiments, using a uniform experimental design, guided by a pseudo-ternary phase diagram, in which the TMP skin permeation level and mean particle size were indices. The effects of MN pretreatment on skin permeation by TMP-ME were assessed using in vitro skin permeation, in vivo skin microdialysis, and pharmacokinetic studies in rats. The influence of MN pretreatment on the skin barrier function was evaluated by measuring the electrical resistance of rat skin before and after MN insertion. In the optimal formulation of TMP-ME, the weight percentages of Maisine^® 35-1 (oil phase), Labrasol^® (surfactant), and Transcutol^® P (co-surfactant) were 7%, 30% and 10%, respectively, with 1.5% TMP loading. In the in vitro skin permeation study, MN-assisted TMP-ME exhibited a two-fold increase in a 24-h cumulative TMP permeation compared with TMP-ME alone (p < 0.05). In the skin microdialysis study, TMP in MN-assisted TMP-ME exhibited a 1.25-fold increase in C_max, a 0.93-fold decrease in T_max, and a 0.88-fold increase in AUC_0–t (p < 0.05). Similarly, in the pharmacokinetic study, TMP in MN-assisted TMP-ME exhibited a 2.11-fold increase in C_max, a 0.67-fold decrease in T_max, and a 1.07-fold increase in AUC_0–t (p < 0.05). The percutaneous electrical resistance of rat skin before and after MN insertion was 850 ± 50 Ω/cm² and 283 ± 104 Ω/cm² respectively, indicating that MN dramatically compromises the skin barrier. These results suggest that MN assistance increases the skin permeation rate and the extent of percutaneous absorption of TMP-ME, and that the mechanism may involve the reversible barrier perturbation effect. The rate and extent of percutaneous absorption of TMP-ME can be significantly enhanced by MN assistance, possibly because MN causes a reversible barrier perturbation effect on skin. Full article

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11 pages, 7994 KiB

Open AccessArticle

Application of an Ultrafine Shearing Method for the Extraction of C-Phycocyanin from Spirulina platensis

by Jianfeng Yu^1,2

¹ Food Engineering & Machinery Group, School of Mechanical Engineering, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, Jiangsu, China

² Jiangsu Key Laboratory of Advanced Food Manufacturing Equipment & Technology, 1800 Lihu Avenue, Wuxi 214122, Jiangsu, China

Molecules 2017, 22(11), 2023; https://doi.org/10.3390/molecules22112023 - 21 Nov 2017

Cited by 19 | Viewed by 6722

Abstract

Cell disruption is an important step during the extraction of C-phycocyanin from Spirulina platensis. An ultrafine shearing method is introduced and combined with soaking and ultrasonication to disrupt the cell walls of S. platensis efficiently and economically. Five kinds of cell disruption [...] Read more.

Cell disruption is an important step during the extraction of C-phycocyanin from Spirulina platensis. An ultrafine shearing method is introduced and combined with soaking and ultrasonication to disrupt the cell walls of S. platensis efficiently and economically. Five kinds of cell disruption method, including soaking, ultrasonication, freezing-thawing, soaking-ultrafine shearing and soaking-ultrafine shearing-ultrasonication were applied to break the cell walls of S. platensis. The effectiveness of cell breaking was evaluated based on the yield of the C-phycocyanin. The results show that the maximum C-phycocyanin yield was 9.02%, achieved by the soaking-ultrafine shearing-ultrasonication method, followed by soaking (8.43%), soaking-ultrafine shearing (8.89%), freezing and thawing (8.34%), and soaking-ultrasonication (8.62%). The soaking-ultrafine shearing-ultrasonication method is a novel technique for breaking the cell walls of S. platensis for the extraction of C-phycocyanin. Full article

(This article belongs to the Collection Bioactive Compounds)

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17 pages, 2115 KiB

Open AccessArticle

Application of Enzymatic Extracts from a CALB Standard Strain as Biocatalyst within the Context of Conventional Biodiesel Production Optimization

by Carlos Luna¹, Diego Luna^1,*

, Felipa M. Bautista¹, Rafael Estevez¹, Juan Calero¹, Alejandro Posadillo², Antonio A. Romero¹ and Enrique D. Sancho³

¹ Department of Organic Chemistry, University of Cordoba (UCO), Cordoba 14014, Spain

² Seneca Green Catalyst S.L., Rabanales XXI/University of Cordoba, Cordoba 14014, Spain

³ Department of Microbiology, University of Cordoba, Campus de Rabanales, Ed. Severo Ochoa, 14014 Cordoba, Spain

Molecules 2017, 22(11), 2025; https://doi.org/10.3390/molecules22112025 - 21 Nov 2017

Cited by 13 | Viewed by 5021

Abstract

The application of biocatalysts in the transesterification process of triglycerides (TG) allows integrating the glycerol in the form of monoglyceride (MG), sharply increasing the yield and the environmental sustainability of the conventional biodiesel production process. This is known as Ecodiesel. To overcome the [...] Read more.

The application of biocatalysts in the transesterification process of triglycerides (TG) allows integrating the glycerol in the form of monoglyceride (MG), sharply increasing the yield and the environmental sustainability of the conventional biodiesel production process. This is known as Ecodiesel. To overcome the inconvenient of the high cost of the currently employed highly purified commercial enzymes, the use of scarcely purified extracts obtained from standard strains of the same species of commercial lipases currently applied in this process is being investigated. Thus, Candida antarctica type B (CALB) was chosen to determine the optimal conditions of culture of this yeast. The standard strain was obtained from the Spanish Type Microbial Cultures Collection (CECT) and has been used to carry out several studies to elucidate its optimum growth conditions. Through a process of lyophilization with prior dialysis of the liquid cultures, the enzymatic extracts were obtained. The different obtained cultures have been applied as biocatalysts in the 1,3-selective transesterification reaction of sunflower oil with ethanol to obtain Ecodiesel (FAEE + MG). Selectivity and reaction yields were obtained by gas chromatography. Acceptable yields are obtained during the reaction time as well as in successive reactions, demonstrating the feasibility of using these CALB enzymatic extracts as biocatalysts. Full article

(This article belongs to the Special Issue Meeting of the Spanish Catalysis Society (SECAT’17))

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35 pages, 9931 KiB

Open AccessFeature PaperReview

Synthesis of Spironucleosides: Past and Future Perspectives

by Raquel G. Soengas^1,*

, Gustavo Da Silva² and Juan Carlos Estévez^3,*

¹ Organic Chemistry Area, University of Almeria, Carretera de Sacramento s/n, 04120 Almería, Spain

² Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal

³ Research Center in Biological Chemistry and Molecular Materials (CIQUS) and Organic Chemistry Department, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain

Molecules 2017, 22(11), 2028; https://doi.org/10.3390/molecules22112028 - 22 Nov 2017

Cited by 16 | Viewed by 8154

Abstract

Spironucleosides are a type of conformationally restricted nucleoside analogs in which the anomeric carbon belongs simultaneously to the sugar moiety and to the base unit. This locks the nucleic base in a specific orientation around the N-glycosidic bond, imposing restrictions on the [...] Read more.

Spironucleosides are a type of conformationally restricted nucleoside analogs in which the anomeric carbon belongs simultaneously to the sugar moiety and to the base unit. This locks the nucleic base in a specific orientation around the N-glycosidic bond, imposing restrictions on the flexibility of the sugar moiety. Anomeric spiro-functionalized nucleosides have gained considerable importance with the discovery of hydantocidin, a natural spironucleoside isolated from fermentation broths of Streptomyces hygroscopicus which exhibits potent herbicidal activity. The biological activity of hydantocidin has prompted considerable synthetic interest in this nucleoside and also in a variety of analogues, since important pharmaceutical leads can be found among modified nucleoside analogues. We present here an overview of the most important advances in the synthesis of spironucleosides. Full article

(This article belongs to the Special Issue Advances in Spiro Compounds)

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21 pages, 1630 KiB

Open AccessReview

Dynamic Docking: A Paradigm Shift in Computational Drug Discovery

by Dario Gioia¹, Martina Bertazzo^1,2, Maurizio Recanatini¹, Matteo Masetti^1,*

and Andrea Cavalli^1,2,*

¹ Department of Pharmacy and Biotechnology, Alma Mater Studiorum—Universita’ di Bologna, via Belmeloro 6, I-40126 Bologna, Italy

² Computational Sciences, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova, Italy

Molecules 2017, 22(11), 2029; https://doi.org/10.3390/molecules22112029 - 22 Nov 2017

Cited by 123 | Viewed by 15327

Abstract

Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also [...] Read more.

Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD) have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking). Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress. Full article

(This article belongs to the Special Issue Frontiers in Computational Chemistry for Drug Discovery)

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13 pages, 5650 KiB

Open AccessArticle

The Rosiglitazone-Like Effects of Vitexilactone, a Constituent from Vitex trifolia L. in 3T3-L1 Preadipocytes

by Atsuyoshi Nishina^1,*, Masaya Itagaki¹, Daisuke Sato², Hirokazu Kimura³, Yasuaki Hirai⁴, Nyunt Phay⁵ and Makoto Makishima⁶

¹ College of Science and Technology, Nihon University, 1-5-1 Kandasurugadai, Chiyoda, Tokyo 101-0062, Japan

² Department of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan

³ School of Medical Technology, Faculty of Health Science, Gunma Paz University, 1-7-1 Tonyamachi, Takasaki, Gunma 370-0006, Japan

⁴ Faculty of Arts and Sciences, Showa University, 4562 Kamiyoshida, Fujiyoshida, Yamanashi 403-0005, Japan

⁵ Botany Department, Pathein University, Main Rd., Pathein, Myanmar

⁶ School of Medicine, Nihon University, 30-1 Oyaguchi-kamicho, Itabashi, Tokyo 173-8610, Japan

Molecules 2017, 22(11), 2030; https://doi.org/10.3390/molecules22112030 - 22 Nov 2017

Cited by 16 | Viewed by 6320

Abstract

The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from [...] Read more.

The increased number of patients with type 2 diabetes (T2D) has become a worldwide problem, and insulin sensitizers such as thiazolidinediones (TZDs) are used as therapeutic agents. We found that extracts of Vitex trifolia L. (V. trifolia), a medicinal plant from Myanmar, induced adipogenesis similar to rosiglitazone (ROS), which is a TZD, in 3T3-L1 preadipocytes. In the present study, we attempted to isolate from V. trifolia those compounds that showed ROS-like effects. Among the extracts of hexane, ethyl acetate, and methanol obtained from V. trifolia, the ethyl acetate extract with the strongest ROS-like effects was purified by various chromatographic methods to obtain three known compounds: vitexilactone (1), vitexicarpin (2) and oleanolic acid (3). Among the isolated compounds, the ROS-like action of 1 was the strongest. The effects of 1 on 3T3-L1 cells during adipogenesis were compared with those of ROS. Both 1 and ROS increased lipid accumulation, the expression of adiponectin and GLUT4 in the cell membrane and decreased both the size of adipocytes and the phosphorylation of IRS-1, ERK1/2 and JNK in 3T3-L1 cells. In contrast, unlike ROS, the induction of proteins involved in lipogenesis was partial. ROS-like effects of 1 in 3T3-L1 cells were suppressed by the addition of bisphenol A diglycidyl ether (BADGE), one of a peroxisome proliferator-activated receptor γ (PPARγ) antagonists, suggesting that the action of 1 on adipocytes is mediated by PPARγ. From the results of the present study, it can be concluded that 1 is a novel insulin sensitizer candidate. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 2865 KiB

Open AccessArticle

New Metabolites of Coumarin Detected in Human Urine Using Ultra Performance Liquid Chromatography/Quadrupole-Time-of-Flight Tandem Mass Spectrometry

by Letícia Paula Leonart, João Cleverson Gasparetto, Flávia Lada Degaut Pontes, Letícia Bonancio Cerqueira, Thais Martins Guimarães De Francisco and Roberto Pontarolo^*

Department of Pharmacy, Federal University of Paraná, Street Pref. Lothário Meissner, 632, 80210-170 Curitiba, Paraná, Brazil

Molecules 2017, 22(11), 2031; https://doi.org/10.3390/molecules22112031 - 22 Nov 2017

Cited by 19 | Viewed by 6758

Abstract

Coumarin (1,2-benzopyrone) is a natural compound whose metabolism in humans was established in the 1970s. However, a new metabolite was recently identified in human plasma, indicating that the metabolism of coumarin has not been completely elucidated. To complement the knowledge of its metabolism, [...] Read more.

Coumarin (1,2-benzopyrone) is a natural compound whose metabolism in humans was established in the 1970s. However, a new metabolite was recently identified in human plasma, indicating that the metabolism of coumarin has not been completely elucidated. To complement the knowledge of its metabolism, a rapid and sensitive method using UPLC-QTOF-MS was developed. A total of 12 metabolites was identified using MetaboLynxTM software, including eight metabolites not previously reported in human urine. The identified biotransformation included hydroxylation, glucuronidation, sulfation, methylation, and conjugation with N-acetylcysteine. The present work demonstrates that the metabolism study of coumarin was incomplete, possibly due to limitations of old techniques. The identification of eight inedited metabolites of such a simple molecule suggests that the information regarding the metabolism of other drugs may also be incomplete, and therefore, new investigations are necessary. Full article

(This article belongs to the Special Issue Versatile Coumarins)

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18 pages, 8430 KiB

Open AccessArticle

W_xC-β-SiC Nanocomposite Catalysts Used in Aqueous Phase Hydrogenation of Furfural

by Jacek Rogowski¹, Mariusz Andrzejczuk², Joanna Berlowska³

, Michal Binczarski¹, Dorota Kregiel³

, Andrzej Kubiak⁴

, Magdalena Modelska¹, Elzbieta Szubiakiewicz¹, Andrei Stanishevsky⁵

, Jolanta Tomaszewska¹ and Izabela Alina Witonska^1,*

¹ Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland

² Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507 Warsaw, Poland

³ Institute of Fermentation Technology and Microbiology, Faculty of Food Science and Biotechnology, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland

⁴ Department of Semiconductor and Optoelectronic Devices, Faculty of Electrical, Electronic, Computer and Control Engineering, Lodz University of Technology, ul. Wolczanska 211/215, 90-924 Lodz, Poland

⁵ Department of Physics, University of Alabama at Birmingham, 1300 University Blvd., Birmingham, AL 35294, USA

Molecules 2017, 22(11), 2033; https://doi.org/10.3390/molecules22112033 - 22 Nov 2017

Cited by 10 | Viewed by 4711

Abstract

This study investigates the effects of the addition of tungsten on the structure, phase composition, textural properties and activities of β-SiC-based catalysts in the aqueous phase hydrogenation of furfural. Carbothermal reduction of SiO₂ in the presence of WO₃ at 1550 °C [...] Read more.

This study investigates the effects of the addition of tungsten on the structure, phase composition, textural properties and activities of β-SiC-based catalysts in the aqueous phase hydrogenation of furfural. Carbothermal reduction of SiO₂ in the presence of WO₃ at 1550 °C in argon resulted in the formation of W_xC-β-SiC nanocomposite powders with significant variations in particle morphology and content of W_xC-tipped β-SiC nano-whiskers, as revealed by TEM and SEM-EDS. The specific surface area (SSA) of the nanocomposite strongly depended on the amount of tungsten and had a notable impact on its catalytic properties for the production of furfuryl alcohol (FA) and tetrahydrofurfuryl alcohol (THFA). Nanocomposite W_xC-β-SiC catalysts with 10 wt % W in the starting mixture had the highest SSA and the smallest W_xC crystallites. Some 10 wt % W nanocomposite catalysts demonstrated up to 90% yield of THFA, in particular in the reduction of furfural derived from biomass, although the reproducible performance of such catalysts has yet to be achieved. Full article

(This article belongs to the Section Green Chemistry)

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14 pages, 1615 KiB

Open AccessArticle

Multicenter (FX)_n/NH₃ Halogen Bonds (X = Cl, Br and n = 1–5). QTAIM Descriptors of the Strength of the X∙∙∙N Interaction

by Gabriel J. Buralli^1,3, Andre N. Petelski^2,3, Nélida M. Peruchena^1,3, Gladis L. Sosa^1,2,3 and Darío J. R. Duarte^1,3,*

¹ Laboratorio de Estructura Molecular y Propiedades (LEMYP), Departamento de Química, Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Avenida Libertad 5460, Corrientes 3400, Argentina

² Grupo de Investigación en Química Teórica y Experimental (QUITEX), Departamento de Ingeniería Química, Facultad Regional Resistencia, Universidad Tecnológica Nacional, French 414, Resistencia 3500, Argentina

³ Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), UNNE-CONICET, Avenida Libertad 5460, Corrientes 3400, Argentina

Molecules 2017, 22(11), 2034; https://doi.org/10.3390/molecules22112034 - 22 Nov 2017

Cited by 16 | Viewed by 5516

Abstract

In the present work an in depth deep electronic study of multicenter XBs (FX)_n/NH₃ (X = Cl, Br and n = 1–5) is conducted. The ways in which X∙∙∙X lateral contacts affect the electrostatic or covalent nature of the X∙∙∙N [...] Read more.

In the present work an in depth deep electronic study of multicenter XBs (FX)_n/NH₃ (X = Cl, Br and n = 1–5) is conducted. The ways in which X∙∙∙X lateral contacts affect the electrostatic or covalent nature of the X∙∙∙N interactions are explored at the CCSD(T)/aug-cc-pVTZ level and in the framework of the quantum theory of atoms in molecules (QTAIM). Calculations show that relatively strong XBs have been found with interaction energies lying between −41 and −90 kJ mol⁻¹ for chlorine complexes, and between −56 and −113 kJ mol⁻¹ for bromine complexes. QTAIM parameters reveal that in these complexes: (i) local (kinetics and potential) energy densities measure the ability that the system has to concentrate electron charge density at the intermolecular X∙∙∙N region; (ii) the delocalization indices [δ(A,B)] and the exchange contribution [V_EX(X,N)] of the interacting quantum atoms (IQA) scheme, could constitute a quantitative measure of the covalence of these molecular interactions; (iii) both classical electrostatic and quantum exchange show high values, indicating that strong ionic and covalent contributions are not mutually exclusive. Full article

(This article belongs to the Special Issue Halogen Bonds and Beyond)

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10 pages, 1317 KiB

Open AccessArticle

A New Synthetic Route to Polyhydrogenated Pyrrolo[3,4-b]pyrroles by the Domino Reaction of 3-Bromopyrrole-2,5-Diones with Aminocrotonic Acid Esters

by Khidmet Shikhaliev¹, Artem Sabynin¹, Valeri Sekirin¹, Michael Krysin^1,*

, Fedor Zubkov²

and Kristina Yankina²

¹ Department of Organic Chemistry, Faculty of Chemistry, Voronezh State University, 1 Universitetskaya sq., Voronezh 394018, Russia

² Department of Organic Chemistry, Faculty of Physics and Mathematics and Natural Sciences, RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russia

Molecules 2017, 22(11), 2035; https://doi.org/10.3390/molecules22112035 - 22 Nov 2017

Viewed by 5490

Abstract

A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular [...] Read more.

A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular nucleophilic addition without recyclyzation of imide cycle. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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14 pages, 1617 KiB

Open AccessArticle

Action of Monomeric/Gemini Surfactants on Free Cells and Biofilm of Asaia lannensis

by Anna Koziróg^1,*

, Dorota Kręgiel¹

and Bogumił Brycki²

¹ Institute of Fermentation Technology and Microbiology, Faculty of Biotechnology and Food Science, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland

² Laboratory of Microbiocides Chemistry, Faculty of Chemistry, Adam Mickiewicz University in Poznan, Umultowska 89b, 61-614 Poznań, Poland

Molecules 2017, 22(11), 2036; https://doi.org/10.3390/molecules22112036 - 22 Nov 2017

Cited by 24 | Viewed by 5297

Abstract

We investigated the biological activity of surfactants based on quaternary ammonium compounds: gemini surfactant hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C6), synthesized by the reaction of N,N-dimethyl-N-dodecylamine with 1,6-dibromohexane, and its monomeric analogue dodecyltrimethylammonium bromide (DTAB). The experiments were performed [...] Read more.

We investigated the biological activity of surfactants based on quaternary ammonium compounds: gemini surfactant hexamethylene-1,6-bis-(N,N-dimethyl-N-dodecylammonium bromide) (C6), synthesized by the reaction of N,N-dimethyl-N-dodecylamine with 1,6-dibromohexane, and its monomeric analogue dodecyltrimethylammonium bromide (DTAB). The experiments were performed with bacteria Asaia lannensis, a common spoilage in the beverage industry. The minimal inhibitory concentration (MIC) values were determined using the tube standard two-fold dilution method. The growth and adhesive properties of bacterial cells were studied in different culture media, and the cell viability was evaluated using plate count method. Both of the surfactants were effective against the bacterial strain, but the MIC of gemini compound was significantly lower. Both C6 and DTAB exhibited anti-adhesive abilities. Treatment with surfactants at or below MIC value decreased the number of bacterial cells that were able to form biofilm, however, the gemini surfactant was more effective. The used surfactants were also found to be able to eradicate mature biofilms. After 4 h of treatment with C6 surfactant at concentration 10 MIC, the number of bacterial cells was reduced by 91.8%. The results of this study suggest that the antibacterial activity of the gemini compound could make it an effective microbiocide against the spoilage bacteria Asaia sp. in both planktonic and biofilm stages. Full article

(This article belongs to the Section Chemical Biology)

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8 pages, 994 KiB

Open AccessArticle

Large-Scale Analysis of Antimicrobial Activities in Relation to Amphipathicity and Charge Reveals Novel Characterization of Antimicrobial Peptides

by Chien-Kuo Wang¹, Ling-Yi Shih² and Kuan Y. Chang^2,*

¹ Department of Biotechnology, Asia University, Taichung 413, Taiwan

² Computational Biology Laboratory, Department of Computer Science & Engineering, National Taiwan Ocean University, Keelung 202, Taiwan

Molecules 2017, 22(11), 2037; https://doi.org/10.3390/molecules22112037 - 22 Nov 2017

Cited by 58 | Viewed by 7629

Abstract

It has been unclear to which antimicrobial activities (e.g., anti-gram-positive bacterial, anti-gram-negative bacterial, antifungal, antiparasitic, and antiviral activities) of antimicrobial peptides (AMPs) a given physiochemical property matters most. This is the first computational study using large-scale AMPs to examine the relationships between antimicrobial [...] Read more.

It has been unclear to which antimicrobial activities (e.g., anti-gram-positive bacterial, anti-gram-negative bacterial, antifungal, antiparasitic, and antiviral activities) of antimicrobial peptides (AMPs) a given physiochemical property matters most. This is the first computational study using large-scale AMPs to examine the relationships between antimicrobial activities and two major physiochemical properties of AMPs—amphipathicity and net charge. The results showed that among all kinds of antimicrobial activities, amphipathicity and net charge best differentiated between AMPs with and without anti-gram-negative bacterial activities. In terms of amphipathicity and charge, all the AMPs whose activities were significantly associated with amphipathicity and net charge were alike except those with anti-gram-positive bacterial activities. Furthermore, the higher the amphipathic value, the greater the proportion of AMPs possessing both antibacterial and antifungal activities. This dose–response-like pattern suggests a possible causal relationship—dual antibacterial and antifungal activities of AMPs may be attributable to amphipathicity. These novel findings could be useful for identifying potent AMPs computationally. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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13 pages, 3512 KiB

Open AccessArticle

Preparation of Vitexin Nanoparticles by Combining the Antisolvent Precipitation and High Pressure Homogenization Approaches Followed by Lyophilization for Dissolution Rate Enhancement

by Chengbo Gu^1,*, Ziwei Liu¹, Xiaohan Yuan², Wang Li¹, Yuangang Zu¹ and Yujie Fu^1,*

¹ Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China

² Life Science and Biotechnique Research Center, Northeast Agricultural University, Harbin 150030, China

Molecules 2017, 22(11), 2038; https://doi.org/10.3390/molecules22112038 - 22 Nov 2017

Cited by 23 | Viewed by 6054

Abstract

Vitexin, a natural flavonoid found in many medicinal plants, is well known for its rich pharmacological activities. However, the poor water solubility of vitexin has limited its therapeutic application. The aim of this study was to prepare the nanoparticles of vitexin by combining [...] Read more.

Vitexin, a natural flavonoid found in many medicinal plants, is well known for its rich pharmacological activities. However, the poor water solubility of vitexin has limited its therapeutic application. The aim of this study was to prepare the nanoparticles of vitexin by combining the antisolvent precipitation (ASP) and high pressure homogenization (HPH) approaches followed by lyophilization for improving the dissolution rate of this poorly water-soluble drug. The effects of main factors influencing the mean particle size (MPS) of vitexin were investigated and optimized. Under optimum conditions, vitexin nanosuspensions with an MPS of 80.5 nm were obtained and then lyophilized to form nanoparticles. The obtained vitexin nanoparticles were further characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mass spectrometry (MS), X-ray powder diffraction (XRPD), gas chromatography (GC) and dissolution testing. The results showed that the nanoparticles of vitexin were converted into an amorphous form, with its chemical structure unchanged. Additionally, the residual dimethyl sulfoxide (DMSO) is lower than the International Conference on Harmonization (ICH) limit for class 3 solvents. The dissolution rate of processed vitexin was significantly higher (5.58-fold) than that of raw drug. Overall, the combinative process we developed is an effective way to produce vitexin nanoparticles with markedly enhanced dissolution rate. Full article

(This article belongs to the Section Nanochemistry)

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24 pages, 4556 KiB

Open AccessArticle

Direct Modification of Microcrystalline Cellulose with Ethylenediamine for Use as Adsorbent for Removal Amitriptyline Drug from Environment

by Roosevelt D. S. Bezerra¹, Régis C. Leal^2,3, Mateus S. da Silva⁴, Alan I. S. Morais⁴, Thiago H. C. Marques¹, Josy A. Osajima⁴

, Andréia B. Meneguin^4,5, Hernane Da S. Barud⁵ and Edson C. da Silva Filho^4,*

¹ Federal Institute of Education, Science and Technology of Piauí, Teresina-Central Campus, IFPI, Teresina 64000-040, PI, Brazil

² Federal Institute of Education, Science and Technology of Rio Grande do Norte, Nova Cruz Campus, IFRN, Nova Cruz 59215-000, RN, Brazil

³ Institute of Chemistry, State University of Campinas, UNICAMP, Barão Geraldo, Campinas 13083-970, SP, Brazil

⁴ Interdisciplinary Laboratory for Advanced Materials-LIMAV, UFPI, Teresina 64049-550, PI, Brazil

⁵ Laboratory of Polymers and Biomaterials (BioPolMat), UNIARA, Araraquara 14801-340, SP, Brazil

Molecules 2017, 22(11), 2039; https://doi.org/10.3390/molecules22112039 - 22 Nov 2017

Cited by 41 | Viewed by 8696

Abstract

Cellulose derivatives have been widely used as adsorbents for the removal of micropollutants such as drugs, dyes, and metals, due to their abundance, low cost and non-contaminating nature. In this context, several studies have been performed searching for new adsorbents (cellulose derivatives) efficient [...] Read more.

Cellulose derivatives have been widely used as adsorbents for the removal of micropollutants such as drugs, dyes, and metals, due to their abundance, low cost and non-contaminating nature. In this context, several studies have been performed searching for new adsorbents (cellulose derivatives) efficient at contaminant removal from aqueous solutions. Thus, a new adsorbent was synthesized by chemical modification of cellulose with ethylenediamine in the absence of solvent and applied to the adsorption of amitriptyline (AMI) in aqueous solution. The modification reaction was confirmed by X-ray Diffraction (XRD), elemental analysis, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetry/Differential Scanning Calorimeter (TG/DSC), solid state Nuclear Magnetic Resonance of ¹H and ¹³C (¹H-NMR and ¹³C-NMR). Moreover, the effectiveness of reaction was confirmed by computational calculations using Density Functional Theory (DFT) at level B3LYP/6-31G(d). This adsorption process was influenced by pH, time, concentration, temperature and did not show significant changes due to the ionic strength variation. Through these experiments, it was observed that the maximum adsorption capacity of AMI by CN polymer at 298 K, 300 min, and pH 7 was 87.66 ± 0.60 mg·g⁻¹. Full article

(This article belongs to the Special Issue Cellulose Chemical Modifications—Towards Sustainable Materials)

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