Molecules

Editorial

3 pages, 139 KiB

Open AccessEditorial

by Ileana Dragutan^1,*,†, Valerian Dragutan^1,*,† and Albert Demonceau^2,*,†

¹ Institute of Organic Chemistry “C.D. Nenitescu”, Romanian Academy, 202B Spl. Independentei, 060023 Bucharest, P.O. Box 35-108, Romania

² Department of Chemistry, University of Liège, Sart-Tilman (B.6a), 4000 Liège, Belgium

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 255; https://doi.org/10.3390/molecules22020255 - 8 Feb 2017

Cited by 10 | Viewed by 4242

Abstract

The organic chemistry of ruthenium has been one of the most vigorously growing research areas over the past decades. Considerable effort has been extended towards the design and application of a broad series of ruthenium complexes, which culminated with the development by Ryoji [...] Read more.

The organic chemistry of ruthenium has been one of the most vigorously growing research areas over the past decades. Considerable effort has been extended towards the design and application of a broad series of ruthenium complexes, which culminated with the development by Ryoji Noyori (2001 Nobel Prize for Chemistry) of chiral ruthenium catalysts for stereoselective hydrogenation reactions [1], and the discovery by Robert H. Grubbs (2005 Nobel Prize for Chemistry) of well-defined ruthenium–
benzylidene catalysts for olefin metathesis [2] [...] Full article

(This article belongs to the Section Organometallic Chemistry)

4 pages, 167 KiB

Open AccessEditorial

Advances of Vibrational Spectroscopic Technologies in Life Sciences

by Christian W. Huck

Institute of Analytical Chemistry and Radiochemistry, CCB-Center for Chemistry and Biomedicine, Innrain 80/82, 6020 Innsbruck, Austria

Molecules 2017, 22(2), 278; https://doi.org/10.3390/molecules22020278 - 13 Feb 2017

Cited by 6 | Viewed by 3439

Abstract

Generally, vibrational spectroscopy enjoys increasing popularity [1].[...] Full article

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

6 pages, 167 KiB

Open AccessEditorial

Drug Design and Discovery: Principles and Applications

by Shu-Feng Zhou^1,* and Wei-Zhu Zhong^2,*

¹ Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian, China

² Gordon Life Science Institute, Belmont, MA 02478, USA

Molecules 2017, 22(2), 279; https://doi.org/10.3390/molecules22020279 - 13 Feb 2017

Cited by 102 | Viewed by 14002

Abstract

Drug discovery is the process through which potential new therapeutic entities are identified, using a combination of computational, experimental, translational, and clinical models (see, e.g., [1,2]).[...] Full article

(This article belongs to the Special Issue Drug Design and Discovery: Principles and Applications)

2 pages, 143 KiB

Open AccessEditorial

Special Issue: Ribosome-Inactivating Proteins—Commemorative Issue in Honor of Professor Fiorenzo Stirpe

by Els J.M. Van Damme

Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium

Molecules 2017, 22(2), 316; https://doi.org/10.3390/molecules22020316 - 18 Feb 2017

Viewed by 4417

Abstract

The family of ribosome-inactivating proteins (RIPs) groups all enzymes (EC.3.2.2.22) with a so-called RIP domain which comprises N-glycosidase activity and enables these proteins to catalytically inactivate ribosomes.[...] Full article

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

Research

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13 pages, 14827 KiB

Open AccessArticle

Preparation of Thermo-Responsive and Cross-Linked Fluorinated Nanoparticles via RAFT-Mediated Aqueous Polymerization in Nanoreactors

by Jiachen Ma^1,2, Luqing Zhang^1,2, Bing Geng^1,2, Umair Azhar^1,2, Anhou Xu^1,* and Shuxiang Zhang^1,2,*

¹ Shandong Provincial Key Laboratory of Fluorine Chemistry and Chemical Materials, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China

² Shandong Engineering Research Center for Fluorinated Material, University of Jinan, Jinan 250022, China

Molecules 2017, 22(2), 152; https://doi.org/10.3390/molecules22020152 - 25 Jan 2017

Cited by 13 | Viewed by 5519

Abstract

In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide-b-N-isopropylacrylamide) (PDMA-b-PNIPAM) that performed a dual function as both a [...] Read more.

In this work, a thermo-responsive and cross-linked fluoropolymer poly(2,2,2-Trifluoroethyl) methacrylate (PTFEMA) was successfully prepared by reversible addition-fragmentation chain transfer (RAFT) mediated aqueous polymerization with a thermo-responsive diblock poly(dimethylacrylamide-b-N-isopropylacrylamide) (PDMA-b-PNIPAM) that performed a dual function as both a nanoreactor and macro-RAFT agent. The cross-linked polymer particles proved to be in a spherical-like structure of about 50 nm in diameter and with a relatively narrow particle size distribution. ¹H-NMR and ¹⁹F-NMR spectra showed that thermo-responsive diblock P(DMA-b-NIPAM) and cross-linked PTFEMA particles were successfully synthesized. Influence of the amount of ammonium persulfate (APS), the molar ratio of monomers to RAFT agent, influence of the amount of cross-linker on aqueous polymerization and thermo-responsive characterization of the particles are investigated. Monomer conversion increased from 44% to 94% with increasing the molar ratio of APS and P(DMA-b-NIPAM) from 1:9 to1:3. As the reaction proceeded, the particle size increased from 29 to 49 nm due to the consumption of TFEMA monomer. The size of cross-linked nanoparticles sharply decreased from 50.3 to 40.5 nm over the temperature range 14–44 °C, suggesting good temperature sensitivity for these nanoparticles. Full article

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11 pages, 3711 KiB

Open AccessArticle

Synthesis, Characterization and Antibacterial Studies of N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide and Its Neodymium(III) and Thallium(III) Complexes

by Lawrence Nnamdi Obasi¹, Uchechukwu Susan Oruma^1,*, Ibrahim Abdulrazak Al-Swaidan², Ponnadurai Ramasami^3,4, Chigozie Julius Ezeorah¹

and Alfred Ezinna Ochonogor¹

¹ Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka 410001, Nigeria

² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

³ Computational Chemistry Group, Department of Chemistry, Faculty of Science, University of Mauritius, Réduit 80837, Mauritius

⁴ Department of Applied Chemistry, University of Johannesburg, Doornfontein Campus, Johannesburg 2028, South Africa

Molecules 2017, 22(2), 153; https://doi.org/10.3390/molecules22020153 - 22 Feb 2017

Cited by 17 | Viewed by 7499

Abstract

N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) was synthesized by condensation reaction of 4-chlorobenzenesulphonyl chloride and 2-aminobenzothiazole in acetone under reflux. Neodymium(III) and thallium(III) complexes of the ligand were also synthesized. Both ligand and metal complexes were characterized using UV-Vis, IR, ¹H- and ¹³C-NMR spectroscopies, [...] Read more.

N-(Benzothiazol-2-yl)-4-chlorobenzenesulphonamide (NBTCS) was synthesized by condensation reaction of 4-chlorobenzenesulphonyl chloride and 2-aminobenzothiazole in acetone under reflux. Neodymium(III) and thallium(III) complexes of the ligand were also synthesized. Both ligand and metal complexes were characterized using UV-Vis, IR, ¹H- and ¹³C-NMR spectroscopies, elemental analysis and molar conductance measurement. IR studies revealed that the ligand is tridentate and coordinates to the metal ions through nitrogen and oxygen atoms of the sulphonamide group and nitrogen atom attached to benzothiazole ring. The neodymium(III) complex displays a coordination number of eight while thallium(III) complex displays a coordination number of six. The ligand and its complexes were screened in vitro for their antibacterial activities against Escherichia coli strains (E. coli 6 and E. coli 13), Proteus species, Staphylococcus aureus and Pseudomonas aeruginosa using the agar well diffusion technique. The synthesized compounds were found to be more active against the microorganisms screened relative to ciprofloxacin, gentamicin and co-trimoxazole. Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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15 pages, 3262 KiB

Open AccessArticle

Synthesis, Modelling, and Anticonvulsant Studies of New Quinazolines Showing Three Highly Active Compounds with Low Toxicity and High Affinity to the GABA-A Receptor

by Mohamed F. Zayed^1,2,*, Saleh K. Ihmaid¹, Hany E. A. Ahmed^1,3, Khaled El-Adl², Ahmed M. Asiri¹ and Abdelsattar M. Omar^2,4

¹ Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah, Al-Munawarah 41477, Saudi Arabia

² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt

³ Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt

⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia

Molecules 2017, 22(2), 188; https://doi.org/10.3390/molecules22020188 - 24 Jan 2017

Cited by 31 | Viewed by 8143

Abstract

Some novel fluorinated quinazolines (5a–j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic [...] Read more.

Some novel fluorinated quinazolines (5a–j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), ¹³C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 2309 KiB

Open AccessArticle

Efficient Synthesis of Novel Pyridine-Based Derivatives via Suzuki Cross-Coupling Reaction of Commercially Available 5-Bromo-2-methylpyridin-3-amine: Quantum Mechanical Investigations and Biological Activities

by Gulraiz Ahmad¹

, Nasir Rasool^1,*, Hafiz Mansoor Ikram¹, Samreen Gul Khan¹, Tariq Mahmood², Khurshid Ayub², Muhammad Zubair¹, Eman Al-Zahrani³, Usman Ali Rana⁴, Muhammad Nadeem Akhtar⁵ and Noorjahan Banu Alitheen^6,*

¹ Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan

² Department of Chemistry, COMSATS Institute of Information Technology, University Road, Tobe Camp, 22060 Abbottabad, Pakistan

³ Chemistry Department, Faculty of Science, Taif University, 888-Taif, Saudi Arabia

⁴ Sustainable Energy Technologies Center, College of Engineering, P.O. Box 800, King Saud University, Riyadh 11421, Saudi Arabia

⁵ Faculty of Industrial Sciences & Technology, University Malaysia Pahang, Lebuhraya Tun, Razak 26300, Kuantan Pahang, Malaysia

⁶ Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, Serdang, Selangor Darul Ehsan 43400, Malaysia

Molecules 2017, 22(2), 190; https://doi.org/10.3390/molecules22020190 - 27 Jan 2017

Cited by 25 | Viewed by 13031

Abstract

The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3 [...] Read more.

The present study describes palladium-catalyzed one pot Suzuki cross-coupling reaction to synthesize a series of novel pyridine derivatives 2a–2i, 4a–4i. In brief, Suzuki cross-coupling reaction of 5-bromo-2-methylpyridin-3-amine (1) directly or via N-[5-bromo-2-methylpyridine-3-yl]acetamide (3) with several arylboronic acids produced these novel pyridine derivatives in moderate to good yield. Density functional theory (DFT) studies were carried out for the pyridine derivatives 2a–2i and 4a–4i by using B3LYP/6-31G(d,p) basis with the help of GAUSSIAN 09 suite programme. The frontier molecular orbitals analysis, reactivity indices, molecular electrostatic potential and dipole measurements with the help of DFT methods, described the possible reaction pathways and potential candidates as chiral dopants for liquid crystals. The anti-thrombolytic, biofilm inhibition and haemolytic activities of pyridine derivatives were also investigated. In particular, the compound 4b exhibited the highest percentage lysis value (41.32%) against clot formation in human blood among all newly synthesized compounds. In addition, the compound 4f was found to be the most potent against Escherichia coli with an inhibition value of 91.95%. The rest of the pyridine derivatives displayed moderate biological activities. Full article

(This article belongs to the Section Medicinal Chemistry)

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20 pages, 1889 KiB

Open AccessArticle

Comparison of Aquitaine and Rioja Red Wines: Characterization of Their Phenolic Composition and Evolution from 2000 to 2013

by Cindy Quaglieri^1,2,†, Noelia Prieto-Perea^3,†, Luis Angel Berrueta³

, Blanca Gallo³, Zurine Rasines-Perea^1,2, Michael Jourdes^1,2 and Pierre-Louis Teissedre^1,2,*

¹ University Bordeaux, ISVV, EA 4577 Œnologie, F-33140 Villenave d’Ornon, France

² INRA, ISVV, USC 1366 Œnologie, F-33140 Villenave d’Ornon, France

³ Departamento de Química Analítica, Facultad de Ciencia y Tecnología, Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 192; https://doi.org/10.3390/molecules22020192 - 24 Jan 2017

Cited by 12 | Viewed by 5748

Abstract

Wine chemical analysis was carried out on 194 commercial blended red wines produced by two major wine-growing areas—the Aquitaine (France) and Rioja (Spain) regions—in order to compare the wines of both regions. Anthocyanins and derived pigments, tannins and derivatives were identified and quantified [...] Read more.

Wine chemical analysis was carried out on 194 commercial blended red wines produced by two major wine-growing areas—the Aquitaine (France) and Rioja (Spain) regions—in order to compare the wines of both regions. Anthocyanins and derived pigments, tannins and derivatives were identified and quantified by HPLC-DAD-ESI-MS/MS (high pressure liquid chromatography coupled to diode array detector and mass spectrometry using the electrospray ionization interface). Mean degree of polymerization (mDP) was determined. The influence of the wine-growing region and the predominance of the properties of some grape varieties used are confirmed by the significant differences observed between both regions. Rioja and Bordeaux “generic” (Bordeaux and Bordeaux-Supérieur appellations) red wines showed the highest anthocyanic content and the highest mDP, as these wines are in a majority made from Merlot (Bordeaux “generic”) and Tempranillo (Rioja). On the contrary, Bordeaux “specific” regions (Blayais, Médoc, Graves, and Libournais) showed the red wines with the highest total phenolic content and tannin concentration, as the predominant grape variety used is Cabernet Sauvignon. A principal component analysis (PCA) and a hierarchical ascendant classification (HAC) suggesting patterns between the chemical parameters and the distribution of the red wines in three groups were proposed. The comparison of the two wine-growing areas also reveals some similarities between the various grape varieties used. A general effect of a progressive decrease in anthocyanins, anthocyanin-derived pigment and tannins is observed for older wines. Full article

(This article belongs to the Section Molecular Diversity)

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10 pages, 395 KiB

Open AccessArticle

Synthesis and Antifungal Activity of Novel Myrtenal-Based 4-Methyl-1,2,4-triazole-thioethers

by Gui-Shan Lin¹, Wen-Gui Duan^1,*, Lin-Xiao Yang¹, Min Huang¹ and Fu-Hou Lei²

¹ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China

² Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Nanning 530008, Guangxi, China

Molecules 2017, 22(2), 193; https://doi.org/10.3390/molecules22020193 - 24 Jan 2017

Cited by 57 | Viewed by 7290

Abstract

A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was [...] Read more.

A series of novel myrtenal derivatives bearing 1,2,4-triazole moiety were designed and synthesized by multi-step reactions in an attempt to develop potent antifungal agents. Their structures were confirmed by using UV-vis, FTIR, NMR, and ESI-MS analysis. Antifungal activity of the target compounds was preliminarily evaluated by the in vitro method against Fusarium oxysporum f. sp. cucumerinum, Physalospora piricola, Alternaria solani, Cercospora arachidicola, and Gibberella zeae at 50 µg/mL. Compounds 6c (R = i-Pr), 6l (R = o-NO₂ Bn), and 6a (R = Et) exhibited excellent antifungal activity against P. piricola with inhibition rates of 98.2%, 96.4%, and 90.7%, respectively, showing better or comparable antifungal activity than that of the commercial fungicide azoxystrobin with a 96.0% inhibition rate, which served as a positive control. Full article

(This article belongs to the Section Medicinal Chemistry)

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12 pages, 1438 KiB

Open AccessArticle

Arsenic Induces p62 Expression to Form a Positive Feedback Loop with Nrf2 in Human Epidermal Keratinocytes: Implications for Preventing Arsenic-Induced Skin Cancer

by Palak Shah^1,2, Elaine Trinh³, Lei Qiang¹, Lishi Xie⁴, Wen-Yang Hu⁴, Gail S. Prins⁴, Jingbo Pi⁵ and Yu-Ying He^1,2,*

¹ Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL 60637, USA

² Committee on Molecular Pathogenesis and Molecular Medicine, University of Chicago, Chicago, IL 60637, USA

³ Department of Biological Sciences and Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA

⁴ Department of Urology, College of Medicine, and University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA

⁵ Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China

Molecules 2017, 22(2), 194; https://doi.org/10.3390/molecules22020194 - 24 Jan 2017

Cited by 35 | Viewed by 8146

Abstract

Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin [...] Read more.

Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin cancer remains poorly understood. Here, we have shown that arsenic induces p62 expression in an autophagy-independent manner in human HaCaT keratinocytes. In mouse skin, chronic arsenic exposure through drinking water increases p62 protein levels in the epidermis. Nrf2 is required for basal and arsenic-induced p62 up-regulation. p62 knockdown reduces arsenic-induced Nrf2 activity, and induces sustained p21 up-regulation. p62 induction is associated with increased proliferation in mouse epidermis. p62 knockdown had little effect on arsenic-induced apoptosis, while it decreased cell proliferation following arsenic treatment. Our findings indicate that arsenic induces p62 expression to regulate the Nrf2 pathway in human keratinocytes and suggest that targeting p62 may help prevent arsenic-induced skin cancer. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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18 pages, 250 KiB

Open AccessArticle

Chemical Characterization and Antioxidant Potential of Wild Ganoderma Species from Ghana

by Mary Obodai¹

, Deborah L. Narh Mensah¹, Ângela Fernandes², Nii Korley Kortei³, Matilda Dzomeku¹, Matthew Teegarden⁴

, Steven J. Schwartz⁴, Lillian Barros^2,5, Juanita Prempeh¹, Richard K. Takli¹ and Isabel C. F. R. Ferreira^2,*

¹ CSIR-Food Research Institute, Mycology Unit, P.O. Box M20, Accra, Ghana

² Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, Bragança 5300-253, Portugal

³ Department of Nutrition and Dietetics, School of Allied Health Sciences, University of Health and Allied Sciences, PMB 31, Ho, Ghana

⁴ Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA

⁵ Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials (LSRE-LCM), Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1134, Bragança 5301-857, Portugal

Molecules 2017, 22(2), 196; https://doi.org/10.3390/molecules22020196 - 25 Jan 2017

Cited by 60 | Viewed by 8027

Abstract

The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1–LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty [...] Read more.

The chemical characterization and antioxidant potential of twelve wild strains of Ganoderma sp. from Ghana, nine (LS1–LS9) of which were found growing wild simultaneously on the same dying Delonix regia tree, were evaluated. Parameters evaluated included the nutritional value, composition in sugars, fatty acids, phenolic and other organic compounds and some vitamins and vitamin precursors. Antioxidant potential was evaluated by investigating reducing power, radical scavenging activity and lipid peroxidation inhibition using five in vitro assays. Protein, carbohydrate, fat, ash and energy contents ranged between 15.7–24.5 g/100 g·dw, 73.31–81.90 g/100 g, 0.48–1.40 g/100 g, 0.68–2.12 g/100 g ash and 396.1–402.02 kcal/100 g, respectively. Fatty acids such as linoleic, oleic and palmitic acids were relatively abundant. Free sugars included rhamnose, fructose, mannitol, sucrose and trehalose. Total tocopherols, organic acids and phenolic compounds’ content ranged between 741–3191 µg/100 g, 77–1003 mg/100 g and 7.6–489 µg/100 g, respectively. There were variations in the β-glucans, ergosterol and vitamin D₂ contents. The three major minerals in decreasing order were K > P > S. Ganoderma sp. strain AM1 showed the highest antioxidant activity. This study reveals, for the first time, chemical characteristics of Ganoderma spp. which grew simultaneously on the same tree. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 5858 KiB

Open AccessArticle

Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice

by Xiaoxue Xu^1,2,†, Zhuanzhuan Zhang^1,2,†, Wenping Wang^1,2, Huiqin Yao^1,2 and Xueqin Ma^1,2,*

¹ Department of Pharmaceutical Analysis, School of Pharmacy, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China

² Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 1160 Shenli Street, Yinchuan 750004, China

^† Both authors contributed equally to this work.

Molecules 2017, 22(2), 197; https://doi.org/10.3390/molecules22020197 - 24 Jan 2017

Cited by 36 | Viewed by 6276

Abstract

Cistanoside A (Cis A), an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized [...] Read more.

Cistanoside A (Cis A), an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized (OVX) mice model and investigated its underlying molecular mechanisms of action. After 12 weeks of orally-administrated intervention, Cis A (20, 40 and 80 mg/kg body weight/day) exhibited significant antiosteoporotic effects on OVX mice, evidenced by enhanced bone strength, bone mineral density and improved trabecular bone microarchitecture. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline (DPD) and cathepsin K, were decreased, and the bioactivity of bone formation marker alkaline phosphatase (ALP) was increased. Mechanistically, Cis A inhibited the expression of TNF-receptor associated factor 6 (TRAF6), an upstream molecule that is shared by both nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways and subsequently suppressed the levels of receptor activators of nuclear factor kappaB ligand (RANKL), downregulated the expression of NF-κB and upregulated osteoprotegerin (OPG), PI3K and Akt, which means Cis A possessed antiosteoporotic activity in ovariectomized mice via TRAF6-mediated NF-kappaB inactivation and PI3K/Akt activation. Put together, we present novel findings that Cis A, by downregulating TRAF6, coordinates the inhibition of NF-κB and stimulation of PI3K/Akt pathways to promote bone formation and prevent bone resorption. These data demonstrated the potential of Cis A as a promising agent for the treatment of osteoporosis disease. Full article

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

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10 pages, 771 KiB

Open AccessArticle

Backstabbing P-gp: Side-Chain Cleaved Ecdysteroid 2,3-Dioxolanes Hyper-Sensitize MDR Cancer Cells to Doxorubicin without Efflux Inhibition

by Attila Hunyadi^1,2,*

, József Csábi¹, Ana Martins^3,†, Joseph Molnár³, Attila Balázs⁴ and Gábor Tóth⁴

¹ Institute of Pharmacognosy, University of Szeged, 6720 Szeged, Hungary

² Interdisciplinary Centre for Natural Products, University of Szeged, Eötvös str. 6, 6720 Szeged, Hungary

³ Department of Medical Microbiology and Immunobiology, University of Szeged, Dóm sq. 9, 6720 Szeged, Hungary

⁴ NMR Group, Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szt. Gellért Sq. 4, H-1111 Budapest, Hungary

^† Current address: Synthetic Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Temesvári krt. 62, 6726 Szeged, Hungary

Molecules 2017, 22(2), 199; https://doi.org/10.3390/molecules22020199 - 25 Jan 2017

Cited by 26 | Viewed by 5355

Abstract

P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild [...] Read more.

P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild to moderate inhibition of P-gp function. Here we report the preparation of a set of substituted 2,3-dioxolane derivatives of poststerone, a known in vivo metabolite of 20-hydroxyecdysone (20E). In contrast with previously studied ecdysteroid dioxolanes, the majority of the new compounds did not inhibit the efflux function of P-gp. Nevertheless, a strong, dose dependent sensitization to doxorubicin was observed on a P-gp transfected cancer cell line and on its susceptible counterpart. We also observed that the MDR cell line was more sensitive to the compounds’ effect than the non-MDR. Our results showed for the first time that the chemo-sensitizing activity of ecdysteroids can be fully independent of functional efflux pump inhibition, and suggest these compounds as favorable leads against MDR cancer. Full article

(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)

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12 pages, 1030 KiB

Open AccessArticle

The Nitrilimine–Alkene Cycloaddition Regioselectivity Rationalized by Density Functional Theory Reactivity Indices

by Giorgio Molteni¹ and Alessandro Ponti^2,*

¹ Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy

² Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via C. Golgi 19, 20133 Milano, Italy

Molecules 2017, 22(2), 202; https://doi.org/10.3390/molecules22020202 - 26 Jan 2017

Cited by 15 | Viewed by 5732

Abstract

Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions [...] Read more.

Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature. We computed DFT reactivity indices at the B3LYP/6-311G(2d,p)//B3LYP/6-31G(d,p) and employed the grand potential stabilization criterion to calculate the preferred regioisomer. Experimental and calculated regioselectivity agree in the vast majority of cases. It was concluded that predominance of a single regioisomer can be obtained by maximizing (i) the chemical potential difference between nitrilimine and alkene and (ii) the local softness difference between the reactive atomic sites within each reactant. Such maximization can be achieved by carefully selecting the substituents on both reactants. Full article

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

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12 pages, 2809 KiB

Open AccessArticle

Essential Oil Extraction, Chemical Analysis and Anti-Candida Activity of Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball—New Approaches

by Mijat Božović^1,2,†

, Stefania Garzoli^2,†

, Manuela Sabatino^1,2

, Federico Pepi², Anna Baldisserotto³

, Elisa Andreotti⁴

, Carlo Romagnoli⁴, Antonello Mai², Stefano Manfredini^3,* and Rino Ragno^1,2,5,*

¹ Rome Center for Molecular Design, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

² Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

³ Department of Life Sciences and Biotechnology, School of Pharmacy and Heath Products, University of Ferrara, Via L. Borsari 46, 44121 Ferrara, Italy

⁴ Department of Life Sciences, University of Modena and Reggio Emilia, Viale Caduti in Guerra 127, 41121 Modena, Italy

⁵ Alchemical Dynamics s.r.l., 00125 Rome, Italy

^† These authors contributed equally to this paper.

Molecules 2017, 22(2), 203; https://doi.org/10.3390/molecules22020203 - 26 Jan 2017

Cited by 41 | Viewed by 8175

Abstract

A comprehensive study on essential oils extracted from different Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball samples from Tarquinia (Italy) is reported. In this study, the 24-h steam distillation procedure for essential oil preparation, in terms of different harvesting and extraction times, [...] Read more.

A comprehensive study on essential oils extracted from different Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) Ball samples from Tarquinia (Italy) is reported. In this study, the 24-h steam distillation procedure for essential oil preparation, in terms of different harvesting and extraction times, was applied. The Gas chromatography–mass spectrometry (GC/MS) analysis showed that C. nepeta (L.) Savi subsp. glandulosa (Req.) Ball essential oils from Tarquinia belong to the pulegone-rich chemotype. The analysis of 44 samples revealed that along with pulegone, some other chemicals may participate in exerting the related antifungal activity. The results indicated that for higher activity, the essential oils should be produced with at least a 6-h steam distillation process. Even though it is not so dependent on the period of harvesting, it could be recommended not to harvest the plant in the fruiting stage, since no significant antifungal effect was shown. The maximum essential oil yield was obtained in August, with the highest pulegone percentage. To obtain the oil with a higher content of menthone, September and October should be considered as the optimal periods. Regarding the extraction duration, vegetative stage material gives the oil in the first 3 h, while material from the reproductive phase should be extracted at least at 6 or even 12 h. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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15 pages, 6756 KiB

Open AccessArticle

Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat

by Bolanle C. Akinwumi^1,2

, Pema Raj^2,3,4, Danielle I. Lee^1,2, Crystal Acosta^2,5, Liping Yu^2,4, Samuel M. Thomas⁶, Kalyanam Nagabhushanam⁷

, Muhammed Majeed^6,7, Neal M. Davies^1,8

, Thomas Netticadan^2,3,4,* and Hope D. Anderson^1,2,5,*

¹ College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB R3E 0T5, Canada

² Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada

³ Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada

⁴ Agriculture and Agri-Food Canada, St. Boniface Hospital Research Centre, 351 Taché Avenue, Winnipeg, MB R2H 2A6, Canada

⁵ Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, 753 McDermot Avenue, Winnipeg, MB R3E 0T6, Canada

⁶ Sami Labs Ltd., Peenya Industrial Area, Bangalore 560058, India

⁷ Sabinsa Corporation, 20 Lake Drive, East Windsor, NJ 08520, USA

⁸ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 2-35, Medical Sciences Building, Edmonton, AL T6G 2H7, Canada

Molecules 2017, 22(2), 204; https://doi.org/10.3390/molecules22020204 - 1 Feb 2017

Cited by 14 | Viewed by 6271

Abstract

Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects [...] Read more.

Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function),and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy. Full article

(This article belongs to the Special Issue Polyphenols and Cardiovascular Disease)

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11 pages, 434 KiB

Open AccessArticle

Identification of Larvicidal Constituents of the Essential Oil of Echinops grijsii Roots against the Three Species of Mosquitoes

by Mei Ping Zhao^1,†, Qi Zhi Liu¹, Qiyong Liu² and Zhi Long Liu^1,*

¹ Department of Entomology, China Agricultural University, Haidian District, Beijing 100193, China

² State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center of Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China

^† Current Address: Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China.

Molecules 2017, 22(2), 205; https://doi.org/10.3390/molecules22020205 - 27 Jan 2017

Cited by 22 | Viewed by 6630

Abstract

The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography‐mass spectrometry (GC‐MS) analysis. [...] Read more.

The screening of Chinese medicinal herbs for insecticidal principles showed that the essential oil of Echinops grijsii Hance roots possessed significant larvicidal activity against mosquitoes. The essential oil was extracted via hydrodistillation and its constituents were determined by gas chromatography‐mass spectrometry (GC‐MS) analysis. GC‐MS analyses revealed the presence of 31 components, with 5‐(3‐buten‐1‐yn‐1‐yl)‐2,2′‐bithiophene (5‐BBT, 27.63%), αterthienyl (α‐T, 14.95%),1,8‐cineole (5.56%) and cis‐β‐ocimene (5.01%) being the four major constituents. Based bioactivity‐directed chromatographic separation of the essential oil led to the isolation of 5‐BBT, 5‐(4‐isovaleroyloxybut‐1‐ynyl)‐2,2′‐bithiophene (5‐IBT) and αT as active compounds. The essential oil of E. grijsii exhibited larvicidal activity against the fourth instar larvae of Aedes albopictus, Anopheles sinensis and Culex pipiens pallens with LC50 values of 2.65 μg/mL, 3.43 μg/mL and 1.47 μg/mL, respectively. The isolated thiophenes, 5‐BBT and 5‐IBT, possessed strong larvicidal activity against the fourth instar larvae of Ae. albopictus(LC50 = 0.34 μg/mL and 0.45 μg/mL, respectively) and An. sinensis(LC50 = 1.36 μg/mL and 5.36 μg/mL, respectively). The two isolated thiophenes also had LC50 values against the fourth instar larvae of C. pipiens pallens of 0.12 μg/mL and 0.33 μg/mL, respectively. The findings indicated that the essential oil of E. grijsii roots and the isolated thiophenes have an excellent potential for use in the control of Ae.albopictus, An. sinensis and C. pipiens pallens larvae and could be used in the search for new, safer and more effective natural compounds as larvicides. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 2236 KiB

Open AccessArticle

Synthesis of 16 New Hybrids from Tetrahydropyrans Derivatives and Morita˗Baylis˗Hillman Adducts: In Vitro Screening against Leishmania donovani

by Suervy Canuto de Oliveira Sousa¹, Juliana Da Câmara Rocha², Tatjana De Souza Lima Keesen², Everton Da Paz Silva¹, Priscilla Anne Castro De Assis^1,3, João Paulo Gomes De Oliveira¹, Saulo Luís Capim⁴, Francisco José Seixas Xavier¹, Bruno Guimarães Marinho⁵, Fábio Pedrosa Lins Silva¹, Claudio Gabriel Lima‐Junior^1,* and Mário Luiz Araújo de Almeida Vasconcellos^1,*

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

² Departamento de Biotecnologia, Universidade Federal da Paraíba, Campus I, João Pessoa, PB 58059‐900, Brazil

³ Unidade Acadêmica de Saúde, Centro de Educação e Saúde, Universidade Federal de Campina Grande, Campus Cuité, Cuité, PB 58175‐000, Brazil

⁴ Instituto Federal de Educação, Ciência e Tecnologia da Bahia, Campus Catu, Barão de Camaçari, Catu, BA 48110‐000, Brazil

⁵ Programa de Pós‐Graduação em Ciências Fisiológicas and Laboratório de Farmacologia, Departamento Ciências Fisiológicas, Instituto de Ciências e Saúde, Universidade Federal Rural do Rio de Janeiro Seropédica, RJ 23890‐000, Brazil

Molecules 2017, 22(2), 207; https://doi.org/10.3390/molecules22020207 - 30 Jan 2017

Cited by 10 | Viewed by 5393

Abstract

Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala‐aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The [...] Read more.

Leishmaniases are a group of neglected tropical diseases (NTDs) caused by protozoan parasites from >20 Leishmania species. Visceral leishmaniasis (VL), also known as kala‐aza, is the most severe form of leishmaniasis, usually fatal in the absence of treatment in 95% of cases. The Morita‐Baylis‐Hillman adducts (MBHAs) are being explored as drug candidates against several diseases, one of them being leishmaniasis. We present here the design, synthesis and in vitro screening against Leishmania donovani of sixteen new molecular hybrids from analgesic/antiinflammatory tetrahydropyrans derivatives and Morita˗Baylis˗Hillman adducts. First, acrylates were synthesized from analgesic/anti‐inflammatory tetrahydropyrans using acrylic acid under TsOH as a catalyst (70–75% yields). After the 16 new MBHAs were prepared in moderate to good yields (60–95%) promoted by microwave irradiation or low temperature (0 °C) in protic and aprotic medium. The hybrids were evaluated in vitro on the promastigote stage of Leishmania donovani by determining their inhibitory concentrations 50% (IC₅₀), 50% hemolysis concentration (HC₅₀), selectivity index (HC₅₀/IC₅₀,), and comparing to Amphotericin B, chosen as the anti‐leishmanial reference drug. The hybrid which presents the bromine atom in its chemical structure presents high leishmanicide activity and the high selectivity index in red blood cells (SI_rb > 180.19), compared with the highly‐toxic reference drug (SI_rb = 33.05), indicating that the bromine hybrid is a promising compound for further biological studies. Full article

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

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16 pages, 2034 KiB

Open AccessArticle

Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives

by Laure-Estelle Cassagnes¹

, Nambinina Rakotoarivelo¹, Serena Sirigu², Pierre Pério¹, Ennaji Najahi¹, Léonard M. G. Chavas², Andrew Thompson², Régis Gayon³

, Gilles Ferry⁴, Jean A. Boutin^4,*, Alexis Valentin¹, Karine Reybier^1,† and Françoise Nepveu^1,†

¹ UMR 152 Pharma-Dev, Université de Toulouse, IRD, UPS, 31062 Toulouse, France

² Synchrotron SOLEIL, L’Orme des Merisiers, BP 48 Saint-Aubin, 91190 Gif sur Yvette CEDEX, France

³ Vectalys S.A., Parc Technologique du Canal, Bâtiment Canal Biotech 2, 3, Rue des Satellites, 31400 Toulouse, France

⁴ Expertise Biotechnologie, Chimie, Biologie, Institut de Recherches Servier, 125, Chemin de Ronde, 78290 Croissy sur Seine, France

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 210; https://doi.org/10.3390/molecules22020210 - 30 Jan 2017

Cited by 6 | Viewed by 5873

Abstract

Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we [...] Read more.

Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we hypothesized that human quinone reductase 2 (hQR2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives. Therefore, we investigated the role of hQR2 in the reduction of indolone derivatives. We analyzed the interaction between hQR2 and several indolone-type derivatives by examining enzymatic kinetics, the substrate/protein complex structure with X-ray diffraction analysis, and the production of free radicals with electron paramagnetic resonance. The reduction of each compound in cells overexpressing hQR2 was compared to its reduction in naïve cells. This process could be inhibited by the specific hQR2 inhibitor, S29434. These results confirmed that the anti-malarial activity of indolone-type derivatives was linked to their ability to serve as hQR2 substrates and not as hQR2 inhibitors as reported for chloroquine, leading to the possibility that substrate of hQR2 could be considered as a new avenue for the design of new antimalarial compounds. Full article

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9 pages, 924 KiB

Open AccessArticle

Application of the Crystalline Sponge Method to Revise the Structure of the Phenalenone Fuliginone

by Robert Brkljača¹, Bernd Schneider²

, William Hidalgo², Felipe Otálvaro³, Felipe Ospina³, Shoukou Lee⁴, Manabu Hoshino⁴, Makoto Fujita⁴ and Sylvia Urban^1,*

¹ School of Science (Applied Chemistry and Environmental Science), RMIT University, GPO Box 2476, Melbourne, Victoria 3001, Australia

² Max‐Planck‐Institute for Chemical Ecology, Beutenberg Campus, Hans‐Knöll‐Str. 8, D‐07745 Jena, Germany

³ Instituto de Química, Síntesis y Biosíntesis de Metabolitos Naturales, Universidad de Antioquia, AA 1226, Medellín, Colombia

⁴ Department of Applied Chemistry, School of Engineering, The University of Tokyo, Hongo, Bunkyo‐ku, Tokyo, 113‐8656, Japan

Molecules 2017, 22(2), 211; https://doi.org/10.3390/molecules22020211 - 30 Jan 2017

Cited by 14 | Viewed by 8228

Abstract

The structure of fuliginone was revised from a phenyl substituted phenalenone to a hydroxyl substituted phenalenone as a result of its re‐purification via HPLC with subsequent NMR analysis together with an independent synthesis and analysis of the crystal structure, which was secured via [...] Read more.

The structure of fuliginone was revised from a phenyl substituted phenalenone to a hydroxyl substituted phenalenone as a result of its re‐purification via HPLC with subsequent NMR analysis together with an independent synthesis and analysis of the crystal structure, which was secured via the crystalline sponge method. On‐flow High Performance Liquid Chromatography coupled to Nuclear Magnetic Resonance spectroscopy (HPLC‐NMR) was employed to confirm the presence of the natural product in the plant extract and to monitor for any possible degradation or conversion of the compound. Full article

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

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16 pages, 1558 KiB

Open AccessArticle

Immobilized Lipases on Functionalized Silica Particles as Potential Biocatalysts for the Synthesis of Fructose Oleate in an Organic Solvent/Water System

by Vinicius Vescovi¹, Raquel L. C. Giordano¹, Adriano A. Mendes^2,*

and Paulo W. Tardioli¹

¹ Postgraduate Program in Chemical Engineering, Department of Chemical Engineering, Federal University of São Carlos, 13565‐905 São Carlos, SP, Brazil

² Institute of Chemistry, Federal University of Alfenas, 37130‐001 Alfenas, MG, Brazil

Molecules 2017, 22(2), 212; https://doi.org/10.3390/molecules22020212 - 30 Jan 2017

Cited by 39 | Viewed by 6148

Abstract

Lipases from Thermomyces lanuginosus (TLL) and Pseudomonas fluorescens (PFL) wereimmobilized on functionalized silica particles aiming their use in the synthesis of fructose oleate in a tert‐butyl alcohol/water system. Silica particles were chemically modified with octyl (OS), octyl plus glutaraldehyde (OSGlu), octyl plus [...] Read more.

Lipases from Thermomyces lanuginosus (TLL) and Pseudomonas fluorescens (PFL) wereimmobilized on functionalized silica particles aiming their use in the synthesis of fructose oleate in a tert‐butyl alcohol/water system. Silica particles were chemically modified with octyl (OS), octyl plus glutaraldehyde (OSGlu), octyl plus glyoxyl(OSGlx), and octyl plus epoxy groups(OSEpx). PFL was hyperactivated on all functionalized supports (more than 100% recovered activity) using low protein loading (1 mg/g), however, for TLL, this phenomenon was observed only using octyl‐silica (OS). All prepared biocatalysts exhibited high stability by incubating in tert‐butyl alcohol (half‐lives around 50 h at 65 °C). The biocatalysts prepared using OS and OSGlu as supports showed excellent performance in the synthesis of fructose oleate. High estersynthesis was observed when a small amount of water (1%, v/v) was added to the organic phase, allowing an ester productivity until five times (0.88–0.96 g/L.h) higher than in the absence of water (0.18–0.34 g/L.h) under fixed enzyme concentration (0.51 IU/g of solvent). Maximum ester productivity (16.1–18.1 g/L.h) was achieved for 30 min of reaction catalyzed by immobilized lipases on OS and OSGlu at 8.4 IU/mL of solvent. Operational stability tests showed satisfactory stability after four consecutive cycles of reaction. Full article

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

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15 pages, 3092 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome

by Liangkun Pan^1,†, Nan Hang^2,†, Chao Zhang¹

, Yu Chen¹, Shuchun Li¹, Yang Sun^2,*, Zhongjun Li¹ and Xiangbao Meng^1,*

¹ State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

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

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 213; https://doi.org/10.3390/molecules22020213 - 30 Jan 2017

Cited by 20 | Viewed by 7666

Abstract

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide‐binding domain leucine‐rich repeat containing protein family，pyrin domain‐containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ‐09 and TBZ‐21, were identified by [...] Read more.

A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide‐binding domain leucine‐rich repeat containing protein family，pyrin domain‐containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ‐09 and TBZ‐21, were identified by antiproduction of IL‐1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti‐inflammatory activities were investigated. Several compounds were identified as anti‐inflammatory agents that can reduce IL‐1β expression in a dosedependent manner. A preliminary structure–activity relationship is also summarized here. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 2085 KiB

Open AccessArticle

Pharmacokinetics Studies of 12 Alkaloids in Rat Plasma after Oral Administration of Zuojin and Fan-Zuojin Formulas

by Ping Qian^1,2, You-Bo Zhang¹, Yan-Fang Yang¹, Wei Xu¹ and Xiu-Wei Yang^1,*

¹ 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

² Department of Pharmacognosy, School of Pharmacy, China Medical University, Shenyang 110122, China

Molecules 2017, 22(2), 214; https://doi.org/10.3390/molecules22020214 - 30 Jan 2017

Cited by 49 | Viewed by 6842

Abstract

Zuojin formula (ZJ) is a traditional Chinese medicine (TCM) prescription consisted of Coptidis Rhizoma (CR) and Euodiae Fructus (EF), and has been used to treat gastrointestinal (GI) disease for more than 700 years. Fan-Zuojin formula (FZJ) is a related TCM prescription also consisted [...] Read more.

Zuojin formula (ZJ) is a traditional Chinese medicine (TCM) prescription consisted of Coptidis Rhizoma (CR) and Euodiae Fructus (EF), and has been used to treat gastrointestinal (GI) disease for more than 700 years. Fan-Zuojin formula (FZJ) is a related TCM prescription also consisted of CR and EF with the opposite proportion. In recent years, ZJ was getting more attention for its antitumor potential, but the indeterminate pharmacokinetic (PK) behavior restricted its clinical applications, and the PK differences between ZJ and FZJ were also largely unknown. Consequently it is necessary to carry out a full-scale PK study to demonstrate the physiological disposition of ZJ, as well as the comparative PK study between ZJ and FZJ to illustrate the compatibility dose effects. Therefore a liquid chromatographic–tandem mass spectrometry (LC–MS/MS) method was established and validated for the determinations of coptisine, epiberberine, palmatine, berberine, 8-oxocoptisine, 8-oxoepiberberine, noroxyhydrastinine, corydaldine, dehydroevodiamine, evodiamine, wuchuyuamide-I, and evocarpine in rat plasma. PK characteristics of 12 alkaloids after oral administration of ZJ and FZJ were compared, and the result was analyzed and discussed with the help of an in silico study. Then an integrated PK study was carried out with the AUC-based weighting method and the total drug concentration method. The established method has been successfully applied to reveal the PK profiles of the 12 alkaloids in rat plasma after oral administration of ZJ and FZJ. The results showed that: (1) double peaks were observed in the plasma concentration-time (C–T) curves of the alkaloids after ZJ administration; but the C–T curves approximately matched the two-compartment model after FZJ administration; (2) There were wide variations in the absorption levels of these alkaloids; and even for a certain alkaloid, the dose modified systemic exposure levels and elimination rate also varied significantly after administration of ZJ and FZJ extracts. The results could be interpreted as follows: firstly, inhibition effect on GI motility caused by the high content CR alkaloids (especially berberine) in ZJ could delay the Tmax, and increase the absorption and systemic exposure levels of the other alkaloids, and also lead to the double peak phenomenon of these alkaloids. However, for quaternary protoberberine alkaloids (QPA), double peaks were primarily caused by the different Ka value in two intestinal absorption sites. Secondly, absorption was the major obstacle to the systemic exposure level of the alkaloids from CR and EF. In silico and PK studies suggested that the absorption of these alkaloids, except QPAs, mainly depended on their solubility rather than permeability. Thirdly, EF could promote the absorption and accelerate the elimination of QPAs, and had a greater influence on the former than the latter. At last the integrated PK analysis suggested that berberine and dehydroevodiamine could be regarded as the representative components to reflect the PK behaviors of CR and EF alkaloids after administration of ZJ and FZJ. In conclusion, the absorption, elimination and systemic exposure level of these alkaloids were mainly influenced by the proportion of EF and CR, the pharmacological effect on GI motility, and the physicochemical property of these alkaloids. These findings would be helpful for a better understanding of the activities and clinical applications of ZJ, FZJ and other related TCM prescriptions. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 1336 KiB

Open AccessArticle

A Novel Convergent Synthesis of the Potent Antiglaucoma Agent Tafluprost

by Małgorzata Krupa¹, Michał Chodyński¹, Anna Ostaszewska¹, Piotr Cmoch^1,2

and Iwona Dams^1,*

¹ Chemistry Department, Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland

² Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 42/52, 01-224 Warsaw, Poland

Molecules 2017, 22(2), 217; https://doi.org/10.3390/molecules22020217 - 31 Jan 2017

Cited by 14 | Viewed by 9012

Abstract

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing [...] Read more.

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia–Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2–5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described. Full article

(This article belongs to the Section Medicinal Chemistry)

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17 pages, 992 KiB

Open AccessArticle

Exploring the Effects of Geographical Origin on the Chemical Composition and Quality Grading of Vitis vinifera L. cv. Chardonnay Grapes

by Joanna M. Gambetta¹, Daniel Cozzolino²

, Susan E.P. Bastian¹ and David W. Jeffery^1,*

¹ School of Agriculture, Food and Wine, Waite Research Institute, The University of Adelaide, PMB 1, Glen Osmond, SA 5064, Australia

² School of Medical and Applied Sciences, Central Queensland Innovation and Research Precinct, Central Queensland University, Bruce Highway, North Rockhampton, QLD 4701, Australia

Molecules 2017, 22(2), 218; https://doi.org/10.3390/molecules22020218 - 31 Jan 2017

Cited by 27 | Viewed by 6556

Abstract

The relationship between berry chemical composition, region of origin and quality grade was investigated for Chardonnay grapes sourced from vineyards located in seven South Australian Geographical Indications (GI). Measurements of basic chemical parameters, amino acids, elements, and free and bound volatiles were conducted [...] Read more.

The relationship between berry chemical composition, region of origin and quality grade was investigated for Chardonnay grapes sourced from vineyards located in seven South Australian Geographical Indications (GI). Measurements of basic chemical parameters, amino acids, elements, and free and bound volatiles were conducted for grapes collected during 2015 and 2016. Multiple factor analysis (MFA) was used to determine the sets of data that best discriminated each GI and quality grade. Important components for the discrimination of grapes based on GI were 2-phenylethanol, benzyl alcohol and C6 compounds, as well as Cu, Zn, and Mg, titratable acidity (TA), total soluble solids (TSS), and pH. Discriminant analysis (DA) based on MFA results correctly classified 100% of the samples into GI in 2015 and 2016. Classification according to grade was achieved based on the results for elements such as Cu, Na, Fe, volatiles including C6 and aryl alcohols, hydrolytically-released volatiles such as (Z)-linalool oxide and vitispirane, pH, TSS, alanine and proline. Correct classification through DA according to grade was 100% for both vintages. Significant correlations were observed between climate, GI, grade, and berry composition. Climate influenced the synthesis of free and bound volatiles as well as amino acids, sugars, and acids, as a result of higher temperatures and precipitation. Full article

(This article belongs to the Section Natural Products Chemistry)

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17 pages, 2433 KiB

Open AccessArticle

The Transcription Profile Unveils the Cardioprotective Effect of Aspalathin against Lipid Toxicity in an In Vitro H9c2 Model

by Rabia Johnson^1,2,*

, Phiwayinkosi V. Dludla^1,2

, Christo J. F. Muller^1,2,3

, Barbara Huisamen^1,2, M. Faadiel Essop⁴ and Johan Louw^1,3

¹ Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa

² Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa

³ Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa 3886, South Africa

⁴ Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7599, South Africa

Molecules 2017, 22(2), 219; https://doi.org/10.3390/molecules22020219 - 31 Jan 2017

Cited by 43 | Viewed by 8214

Abstract

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect [...] Read more.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocyte model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 h before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, CD36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results suggest that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis. Full article

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

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18 pages, 1141 KiB

Open AccessArticle

Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors

by Karla Fabiola Chacón-Vargas^1,2

, Benjamin Nogueda-Torres², Luvia E. Sánchez-Torres¹

, Erick Suarez-Contreras², Juan Carlos Villalobos-Rocha²

, Yuridia Torres-Martinez³, Edgar E. Lara-Ramirez³, Giulia Fiorani^4,5, R. Luise Krauth-Siegel⁴, Maria Laura Bolognesi⁵

, Antonio Monge⁶ and Gildardo Rivera^3,*

¹ Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala, s/n, 11340 Ciudad de México, México

² Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala, s/n, 11340 Ciudad de México, México

³ Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elías Piña, 88710 Reynosa, México

⁴ Center of Biochemistry, Heidelberg University, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany

⁵ Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy

⁶ Neglected Diseases Section, Drug R&D Unit, Center for Applied Pharmacobiology Research, University of Navarra, 31008 Pamplona, Spain

Molecules 2017, 22(2), 220; https://doi.org/10.3390/molecules22020220 - 1 Feb 2017

Cited by 36 | Viewed by 6668

Abstract

Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a [...] Read more.

Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity. Full article

(This article belongs to the Section Medicinal Chemistry)

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11 pages, 4634 KiB

Open AccessArticle

Enhanced Performance of Magnetic Graphene Oxide-Immobilized Laccase and Its Application for the Decolorization of Dyes

by Jing Chen, Juan Leng, Xiai Yang, Liping Liao, Liangliang Liu^* and Aiping Xiao^*

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

Molecules 2017, 22(2), 221; https://doi.org/10.3390/molecules22020221 - 1 Feb 2017

Cited by 73 | Viewed by 6995

Abstract

In this study, magnetic graphene oxide (MGO) nanomaterials were synthesized based on covalent binding of amino Fe3O4 nanoparticles onto the graphene oxide (GO), and the prepared MGO was successfully applied as support for the immobilization of laccase. The MGO-laccase was characterized by transmission [...] Read more.

In this study, magnetic graphene oxide (MGO) nanomaterials were synthesized based on covalent binding of amino Fe3O4 nanoparticles onto the graphene oxide (GO), and the prepared MGO was successfully applied as support for the immobilization of laccase. The MGO-laccase was characterized by transmission electron microscopy (TEM) and a vibrating sample magnetometer (VSM). Compared with free laccase, the MGO-laccase exhibited better pH and thermal stabilities. The optimum pH and temperature were confirmed as pH 3.0 and 35 °C. Moreover, the MGO-laccase exhibited sufficient magnetic response and satisfied reusability after being retained by magnetic separation. The MGO-laccase maintained 59.8% activity after ten uses. MGO-laccase were finally utilized in the decolorization of dye solutions and the decolorization rate of crystal violet (CV), malachite green (MG), and brilliant green (BG) reached 94.7% of CV, 95.6% of MG, and 91.4% of BG respectively. The experimental results indicated the MGO-laccase nanomaterials had a good catalysis ability to decolorize dyes in aqueous solution. Compared with the free enzyme, the employment of MGO as enzyme immobilization support could efficiently enhance the availability and facilitate the application of laccase. Full article

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10 pages, 590 KiB

Open AccessArticle

The Essential Oil of Monarda didyma L. (Lamiaceae) Exerts Phytotoxic Activity in Vitro against Various Weed Seed

by Donata Ricci¹, Francesco Epifano² and Daniele Fraternale^1,*

¹ Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino Carlo Bo, sez. Biologia Vegetale, via Bramante 28 61029 Urbino (PU), Italy

² Dipartimento di Farmacia, Università degli Studi di Chieti-Pescara G. d’Annunzio, via dei Vestini 31 66100 Chieti (CH), Italy

Molecules 2017, 22(2), 222; https://doi.org/10.3390/molecules22020222 - 2 Feb 2017

Cited by 32 | Viewed by 7694

Abstract

The chemical composition of the essential oil of the flowering aerial parts of Monarda didyma L. cultivated in central Italy was analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). The major compounds of the oil were thymol (59.3%), p-cymene (10.3%), terpinolene (9.2%), δ-3-carene (4.4%), myrcene [...] Read more.

The chemical composition of the essential oil of the flowering aerial parts of Monarda didyma L. cultivated in central Italy was analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). The major compounds of the oil were thymol (59.3%), p-cymene (10.3%), terpinolene (9.2%), δ-3-carene (4.4%), myrcene (3.7%), and camphene (3.4%). The essential oil was tested in vitro for its anti-germination activity against Papaver rhoeas L., Taraxacum officinale F. H. Wigg., Avena fatua L., Raphanus sativus L. and Lepidium sativum L. seeds, demonstrating good inhibitory activity in a dose-dependent way. The exposure of the employed weed seeds to M. didyma essential oil and thymol solution (59.3%) increased the level of hydrogen peroxide (H2O2) and malondialdehyde (MDA), markers of oxidative stress, in emerging 5-day-old rootlets. Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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20 pages, 2231 KiB

Open AccessArticle

Synthesis of Novel Pyrazinamide Derivatives Based on 3-Chloropyrazine-2-carboxamide and Their Antimicrobial Evaluation

by Ondrej Jandourek^1,*

, Marek Tauchman², Pavla Paterova³, Klara Konecna¹

, Lucie Navratilova⁴, Vladimir Kubicek⁵, Ondrej Holas⁶, Jan Zitko²

and Martin Dolezal²

¹ Department of Biological and Medical Sciences, Teaching and Research Center of Charles University, Faculty of Pharmacy in Hradec Kralove, Charles University, Zborovska 2089, Hradec Kralove 50003, Czech Republic

² Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203/8, Hradec Kralove 50005, Czech Republic

³ Department of Clinical Microbiology, University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove 50005, Czech Republic

⁴ Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203/8, Hradec Kralove 50005, Czech Republic

⁵ Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203/8, Hradec Kralove 50005, Czech Republic

⁶ Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University, Akademika Heyrovskeho 1203/8, Hradec Kralove 50005, Czech Republic

Molecules 2017, 22(2), 223; https://doi.org/10.3390/molecules22020223 - 2 Feb 2017

Cited by 15 | Viewed by 7356

Abstract

Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37Rv that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42 [...] Read more.

Aminodehalogenation of 3-chloropyrazine-2-carboxamide with variously substituted benzylamines yielded a series of fifteen 3-benzylaminopyrazine-2-carboxamides. Four compounds possessed in vitro whole cell activity against Mycobacterium tuberculosis H37Rv that was at least equivalent to that of the standard pyrazinamide. MIC values ranged from 6 to 42 μM. The best MIC (6 μM) was displayed by 3-[(4-methylbenzyl)amino]pyrazine-2-carboxamide (8) that also showed low cytotoxicity in the HepG2 cell line (IC50 ≥ 250 μM). Only moderate activity against Enterococcus faecalis and Staphylococcus aureus was observed. No activity was detected against any of tested fungal strains. Molecular docking with mycobacterial enoyl-ACP reductase (InhA) was performed to investigate the possible target of the prepared compounds. Active compounds shared common binding interactions of known InhAinhibitors. Antimycobacterial activity of the title compounds was compared to the previously published benzylamino-substituted pyrazines with differing substitution on the pyrazine core (carbonitrile moiety). The title series possessed comparable activity and lower cytotoxicity than molecules containing a carbonitrile group on the pyrazine ring. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 431 KiB

Open AccessArticle

Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

by Emmy Tuenter^1,*

, Karen Segers², Kyo Bin Kang³

, Johan Viaene², Sang Hyun Sung³

, Paul Cos⁴

, Louis Maes⁴

, Yvan Vander Heyden² and Luc Pieters¹

¹ Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium

² Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research (CePhaR), Vrije Universiteit Brussel—VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium

³ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea

⁴ Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium

Molecules 2017, 22(2), 224; https://doi.org/10.3390/molecules22020224 - 2 Feb 2017

Cited by 24 | Viewed by 6246

Abstract

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more [...] Read more.

Cyclopeptide alkaloids are polyamidic, macrocyclic compounds, containing a 13-, 14-, or 15-membered ring. The ring system consists of a hydroxystyrylamine moiety, an amino acid, and a β-hydroxy amino acid; attached to the ring is a side chain, comprised of one or two more amino acid moieties. In vitro antiplasmodial activity was shown before for several compounds belonging to this class, and in this paper the antiplasmodial and cytotoxic activities of ten more cyclopeptide alkaloids are reported. Combining these results and the IC50 values that were reported by our group previously, a library consisting of 19 cyclopeptide alkaloids was created. A qualitative SAR (structure-activity relationship) study indicated that a 13-membered macrocyclic ring is preferable over a 14-membered one. Furthermore, the presence of a β-hydroxy proline moiety could correlate with higher antiplasmodial activity, and methoxylation (or, to a lesser extent, hydroxylation) of the styrylamine moiety could be important for displaying antiplasmodial activity. In addition, QSAR (quantitative structure-activity relationship) models were developed, using PLS (partial least squares regression) and MLR (multiple linear regression). On the one hand, these models allow for the indication of the most important descriptors (molecular properties) responsible for the antiplasmodial activity. Additionally, predictions made for interesting structures did not contradict the expectations raised in the qualitative SAR study. Full article

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

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9 pages, 280 KiB

Open AccessArticle

Chemical Reactivity Theory Study of Advanced Glycation Endproduct Inhibitors

by Juan Frau¹

and Daniel Glossman-Mitnik^1,2,*

¹ Departament de Química, Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain

² Laboratorio Virtual NANOCOSMOS, Centro de Investigación en Materiales Avanzados, Departamento de Medio Ambiente y Energía, Chihuahua, Chih 31136, Mexico

Molecules 2017, 22(2), 226; https://doi.org/10.3390/molecules22020226 - 2 Feb 2017

Cited by 26 | Viewed by 5371

Abstract

Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of anumberofdensityfunctionalswhoseaccuracyhasbeentestedacrossabroadspectrumofdatabases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through [...] Read more.

Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of anumberofdensityfunctionalswhoseaccuracyhasbeentestedacrossabroadspectrumofdatabases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through Conceptual DFT in an attempt to relate their intrinsic chemical reactivity with the ability to inhibit the action of glycating carbonyl compounds on amino acids and proteins. This knowledge could be useful in the design and development of new drugs which can be potential medicines for diabetes and Alzheimer’s disease. Full article

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

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16 pages, 1982 KiB

Open AccessArticle

Theoretical Study of Intramolecular Interactions in Peri-Substituted Naphthalenes: Chalcogen and Hydrogen Bonds

by Goar Sánchez–Sanz¹, Ibon Alkorta^2,*

and José Elguero²

¹ Irish Centre of High-End Computing, Grand Canal Quay, Dublin 2, Ireland

² Instituto de Química Médica, CSIC, Juan de la Cierva, 3, E–28006 Madrid, Spain

Molecules 2017, 22(2), 227; https://doi.org/10.3390/molecules22020227 - 2 Feb 2017

Cited by 25 | Viewed by 7442

Abstract

A theoretical study of the peri interactions, both intramolecular hydrogen (HB) and chalcogen bonds (YB), in 1-hydroxy-8YH-naphthalene, 1,4-dihydroxy-5,8-di-YH-naphthalene, and 1,5-dihydroxy-4,8-di-YH-naphthalene, with Y = O, S, and Se was carried out. The systems with a OH:Y hydrogen bond are the most stable ones followed [...] Read more.

A theoretical study of the peri interactions, both intramolecular hydrogen (HB) and chalcogen bonds (YB), in 1-hydroxy-8YH-naphthalene, 1,4-dihydroxy-5,8-di-YH-naphthalene, and 1,5-dihydroxy-4,8-di-YH-naphthalene, with Y = O, S, and Se was carried out. The systems with a OH:Y hydrogen bond are the most stable ones followed by those with a chalcogen O:Y interaction, those with a YH:O hydrogen bond (Y = S and Se) being the least stable ones. The electron density values at the hydrogen bond critical points indicate that they have partial covalent character. Natural Bond Orbital (NBO) analysis shows stabilization due to the charge transfer between lone pair orbitals towards empty Y-H that correlate with the interatomic distances. The electron density shift maps and non-covalent indexes in the different systems are consistent with the relative strength of the interactions. The structures found on the CSD were used to compare the experimental and calculated results. Full article

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

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14 pages, 1689 KiB

Open AccessArticle

Extraction of Fenugreek (Trigonella foenum-graceum L.) Seed Oil Using Subcritical Butane: Characterization and Process Optimization

by Ling-Biao Gu¹, Xiao-Ning Liu¹, Hua-Min Liu^2,*, Hui-Li Pang^1,* and Guang-Yong Qin¹

¹ School of Physics and Engineering, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, Henan Province, China

² College of Food Science and Technology, Henan University of Technology, 100 Lianhua Road, Zhengzhou 450001, Henan Province, China

Molecules 2017, 22(2), 228; https://doi.org/10.3390/molecules22020228 - 2 Feb 2017

Cited by 54 | Viewed by 10310

Abstract

In this study, the subcritical butane extraction process of fenugreek seed oil was optimized using response surface methodology with a Box-Behnken design. The optimum conditions for extracted oil from fenugreek seed was as follows: extraction temperature of 43.24 °C , extraction time of [...] Read more.

In this study, the subcritical butane extraction process of fenugreek seed oil was optimized using response surface methodology with a Box-Behnken design. The optimum conditions for extracted oil from fenugreek seed was as follows: extraction temperature of 43.24 °C , extraction time of 32.80 min, and particle size of 0.26 mm. No significant differences were found between the experimental and predicted values. The physical and chemical properties of the oil showed that the oil could be used as edible oil. Fatty acid composition of oils obtained by subcritical butane under the optimum conditions and by accelerated solvent extraction showed negligible difference. The oils were rich in linoleic acid (42.71%–42.80%), linolenic acid (26.03%-26.15%), and oleic acid (14.24%-14.40%). The results revealed that the proposed method was feasible, and this essay shows the way to exploit fenugreek seeds by subcritical butane extraction under the scope of edible oils. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

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13 pages, 2869 KiB

Open AccessArticle

An Efficient Method for the Preparative Isolation and Purification of Flavonoid Glycosides and Caffeoylquinic Acid Derivatives from Leaves of Lonicera japonica Thunb. Using High Speed Counter-Current Chromatography (HSCCC) and Prep-HPLC Guided by DPPH-HPLC Experiments

by Daijie Wang¹, Ning Du², Lei Wen¹, Heng Zhu¹, Feng Liu¹, Xiao Wang^1,*

, Jinhua Du^3,*

and Shengbo Li⁴

¹ Shandong Analysis and Test Center, Shandong Academy of Sciences, 19 Keyuan Street, Jinan 250014, China

² Beijing Centre for Physical and Chemical Analysis, Beijing 100089, China

³ College of Food Science and Engineering, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China

⁴ Shandong Yate Eco-Tech Co. Ltd., Linyi 266071, China

Molecules 2017, 22(2), 229; https://doi.org/10.3390/molecules22020229 - 2 Feb 2017

Cited by 41 | Viewed by 7948

Abstract

In this work, the n-butanol extract from leaves of Lonicera japonica Thunb. (L. japonica) was reacted with DPPH and subjected to a HPLC analysis for the guided screening antioxidants (DPPH-HPLC experiments). Then, nine antioxidants, including flavonoid glycosides and caffeoylquinic acid derivatives, were isolated [...] Read more.

In this work, the n-butanol extract from leaves of Lonicera japonica Thunb. (L. japonica) was reacted with DPPH and subjected to a HPLC analysis for the guided screening antioxidants (DPPH-HPLC experiments). Then, nine antioxidants, including flavonoid glycosides and caffeoylquinic acid derivatives, were isolated and purified from leaves of L. japonica using high speed counter-current chromatography (HSCCC) and prep-HPLC. The n-butanol extract was firstly isolated by HSCCC using methyl tert-butyl ether/n-butanol/acetonitrile/water (0.5% acetic acid) (2:2:1:5, v/v), yielding five fractions F1, F2 (rhoifolin), F3 (luteoloside), F4 and F5 (collected from the column after the separation). The sub-fractions F1, F4 and F5 were successfully separated by prep-HPLC. Finally, nine compounds, including chlorogenic acid (1), lonicerin (2), rutin (3), rhoifolin (4), luteoloside (5), 3,4-Odicaffeoylquinic acid (6), hyperoside (7), 3,5-O-dicaffeoylquinic acid (8), and 4,5-O-dicaffeoylquinic acid (9) were obtained, respectively, with the purities over 94% as determined by HPLC. The structures were identified by electrospray ionization mass spectrometry (ESI-MS), 1H- and 13C-NMR. Antioxidant activities were tested, and the isolated compounds showed strong antioxidant activities. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 4052 KiB

Open AccessArticle

Construction and Biological Evaluation of a Novel Integrin α_νβ₃-Specific Carrier for Targeted siRNA Delivery In Vitro

by Xueqi Chen

, Meng Liu^*

, Rongfu Wang^*, Ping Yan, Chunli Zhang, Chao Ma and Lei Yin

Department of Nuclear Medicine, Peking University First Hospital, No. 8, Xishiku St., West District, Beijing 100034, China

Molecules 2017, 22(2), 231; https://doi.org/10.3390/molecules22020231 - 4 Feb 2017

Cited by 6 | Viewed by 5990

Abstract

(1) Background: The great potential of RNA interference (RNAi)-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs) to target tissues and cells. Hence, we aimed at developing and examining a novel integrin α_vβ₃-specific delivery [...] Read more.

(1) Background: The great potential of RNA interference (RNAi)-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs) to target tissues and cells. Hence, we aimed at developing and examining a novel integrin α_vβ₃-specific delivery carrier for targeted transfection of siRNA to malignant tumor cells; (2) Methods: Arginine-glycine-aspartate motif (RGD) was adopted as a tissue target for specific recognition of integrin α_vβ₃. To enable siRNA binding, a chimeric peptide was synthesized by adding nonamer arginine residues (9R) at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD)₂-9R. The efficiency of 9R peptide transferring siRNA was biologically evaluated in vitro by flow cytometry, confocal microscopy, and Western blot; (3) Results: An optimal 10:1 molar ratio of c(RGD)₂-9R to siRNA was confirmed by the electrophoresis on agarose gels. Both the flow cytometry and confocal microscopy results testified that transfection of c(RGD)₂-9R as an siRNA delivery carrier was obviously higher than the naked-siRNA group. The results of Western blot demonstrated that these 9R peptides were able to transduce siRNA to HepG2 cells in vitro, resulting in efficient gene silencing; and (4) Conclusion: The chimeric peptide of c(RGD)₂-9R can be developed as an effective siRNA delivery carrier and shows potential as a new strategy for RNAi-based gene therapy. Full article

(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)

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21 pages, 3522 KiB

Open AccessArticle

Response Surface Methodology Optimization of Ultrasonic-Assisted Extraction of Acer Truncatum Leaves for Maximal Phenolic Yield and Antioxidant Activity

by Lingguang Yang^†, Peipei Yin^†, Hang Fan, Qiang Xue, Ke Li, Xiang Li, Liwei Sun^*

and Yujun Liu^*

¹ National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, China

^† These authors contributed equally to this paper.

Molecules 2017, 22(2), 232; https://doi.org/10.3390/molecules22020232 - 4 Feb 2017

Cited by 74 | Viewed by 9309

Abstract

This study is the first to report the use of response surface methodology to improve phenolic yield and antioxidant activity of Acer truncatum leaves extracts (ATLs) obtained by ultrasonic-assisted extraction. The phenolic composition in ATLs extracted under the optimized conditions were characterized by [...] Read more.

This study is the first to report the use of response surface methodology to improve phenolic yield and antioxidant activity of Acer truncatum leaves extracts (ATLs) obtained by ultrasonic-assisted extraction. The phenolic composition in ATLs extracted under the optimized conditions were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol:water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic bath temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent/100 g d.w. and a maximal DPPH• antioxidant activity of 74,241.61 μmol Trolox equivalent/100 g d.w. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic components in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloylglucoside was proposed. All these results provide practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research. Full article

(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)

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16 pages, 2181 KiB

Open AccessArticle

Characterization of Polysaccharides with Antioxidant and Hepatoprotective Activities from the Edible Mushroom Oudemansiella radicata

by Qin Liu^1,2, Mengjuan Zhu³, Xueran Geng⁴, Hexiang Wang^2,* and Tzi Bun Ng^5,*

¹ Institute of Plant Nutrition, Agricultural Resources and Environmental Science, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China

² State Key Laboratory for Agrobiotechnology, Department of Microbiology, China Agricultural University, Beijing 100193, China

³ Department of Fungal Resource, College of Plant Protection, Shandong Agricultural University, Tai’an 271018, China

⁴ College of Food Science and Engineering, Shanxi Agricultural University, Taigu 030801, China

⁵ School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong 999077, China

Molecules 2017, 22(2), 234; https://doi.org/10.3390/molecules22020234 - 4 Feb 2017

Cited by 72 | Viewed by 7880

Abstract

The preliminary structure, in vitro antioxidant and in vivo hepatoprotective activities of water-soluble polysaccharides (ORWP) and alkali-soluble polysaccharides (ORAP), prepared from the mushroom Oudemansiella radicata, were investigated. Both ORWP and ORAP were heteropolysaccharides with mannose, glucose and galactose being the main monosaccharide [...] Read more.

The preliminary structure, in vitro antioxidant and in vivo hepatoprotective activities of water-soluble polysaccharides (ORWP) and alkali-soluble polysaccharides (ORAP), prepared from the mushroom Oudemansiella radicata, were investigated. Both ORWP and ORAP were heteropolysaccharides with mannose, glucose and galactose being the main monosaccharide components. Regarding the antioxidant activities, ORWP and ORAP showed effective 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity and lipid peroxidation inhibitory effects, as well as moderate reducing power and Fe²⁺ chelating activity. For the hepatoprotective activity, administration of ORWP and ORAP prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities in a carbon tetrachloride-induced acute liver damage model, suppressed hepatic malondialdehyde formation and stimulated the activities of hepatic superoxide dismutase and glutathione peroxidase. Thus, we speculate that ORWP and ORAP may protect the liver from CCl₄-induced hepatic damage via antioxidant mechanisms. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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12 pages, 1233 KiB

Open AccessArticle

Bioactive Benzofuran Derivatives from Cortex Mori Radicis, and Their Neuroprotective and Analgesic Activities Mediated by mGluR₁

by Ya-Nan Wang¹, Mao-Feng Liu¹, Wei-Zhen Hou¹, Rui-Ming Xu¹, Jie Gao², An-Qi Lu¹, Mei-Ping Xie¹, Lan Li¹, Jian-Jun Zhang¹, Ying Peng¹, Li-Li Ma³, Xiao-Liang Wang¹, Jian-Gong Shi¹ and Su-Juan Wang^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, Beijing 100050, China

² GRU Cancer Center, Augusta University, Augusta, GA 30912, USA

³ Editorial Department, Shenyang Pharmaceutical University, Shenyang 110016, China

Molecules 2017, 22(2), 236; https://doi.org/10.3390/molecules22020236 - 8 Feb 2017

Cited by 37 | Viewed by 7343

Abstract

Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-l-arabinopyranoside (1 [...] Read more.

Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3′-O-α-l-arabinopyranoside (1), (9R)-moracin P 9-O-β-d-glucopyranoside (2), (9R)-moracin P 3′-O-β-d-glucopyranoside (3), and (9R)-moracin O 10-O-β-d-glucopyranoside (4) based on the spectroscopic interpretation and chemical analysis. Three benzofuran-type stilbenes, moracin O (5), R (7), and P (8) showed significant neuroprotective activity against glutamate-induced cell death in SK-N-SH cells. In addition, moracin O (5) and P (8) also demonstrated a remarkable inhibition of the acetic acid-induced pain. The molecular docking with metabotropic glutamate receptor 1 (mGluR₁) results indicated that these neuroprotective benzofuran-type stilbenes might be the active analgesic components of the genus Morus, and acted by mediating the mGluR₁ pathway. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 3530 KiB

Open AccessArticle

Changbai Mountain Ginseng (Panax ginseng C.A. Mey) Extract Supplementation Improves Exercise Performance and Energy Utilization and Decreases Fatigue-Associated Parameters in Mice

by Guo-Dong Ma¹, Chun-Hui Chiu^2,†, Yi-Ju Hsu^3,†, Chien-Wen Hou⁴, Yi-Ming Chen^3,* and Chi-Chang Huang^3,*

¹ Sport Science College, Jilin Sport University, Changchun 130022, Jilin, China

² Graduate Institute of Health Industry Technology, Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan

³ Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan 33301, Taiwan

⁴ Laboratory of Exercise Biochemistry, Department of Sports Sciences, University of Taipei, Taipei 11153, Taiwan

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 237; https://doi.org/10.3390/molecules22020237 - 5 Feb 2017

Cited by 55 | Viewed by 11245

Abstract

Changbai Mountain Ginseng (CMG, Panax ginseng C.A. Mey) is a traditional medicine commonly found in Northeast China and grows at elevations of 2000 m or higher in the Changbai Mountain Range. CMG, considered to be a “buried treasure medicine”, is priced higher than [...] Read more.

Changbai Mountain Ginseng (CMG, Panax ginseng C.A. Mey) is a traditional medicine commonly found in Northeast China and grows at elevations of 2000 m or higher in the Changbai Mountain Range. CMG, considered to be a “buried treasure medicine”, is priced higher than other types of ginseng. However, few studies have demonstrated the effects of CMG supplementation on exercise performance, physical fatigue, and the biochemical profile. The major compound of CMG extract was characterized by electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Male ICR mice were divided into 3 groups, the vehicle, CMG-1X and CMG-5X groups (n = 8 per group), and respectively administered 0, 5, or 25 mg/kg/day of CMG extract orally for four weeks. HPLC-ESI-MS/MS results showed that the major compound in CMG extract is ginsenoside Ro. CMG extract significantly increased muscle weight and relative muscle weight (%). CMG extract supplementation dose-dependently increased grip strength (p < 0.0001) and endurance swimming time, decreased levels of serum lactate (p < 0.0001), ammonia (p < 0.0001), creatine kinase (CK, p = 0.0002), and blood urea nitrogen (p < 0.0001), and economized glucose levels (p < 0.0001) after acute exercise challenge. The glycogen in the gastrocnemius muscle was significantly increased with CMG extract treatment. Biochemical profile results showed that creatinine and triacylglycerol significantly decreased and total protein and glucose increased with CMG treatment. This is the first report that CMG extract supplementation increases muscle mass, improves exercise performance and energy utilization, and decreases fatigue-associated parameters in vivo. The major component of CMG extract is ginsenoside Ro, which could be a potential bioactive compound for use as an ergogenic aid ingredient by the food industry. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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10 pages, 507 KiB

Open AccessArticle

Synthesis and Antitumor Activities of Chiral Dipeptide Thioureas Containing an Alpha-Aminophosphonate Moiety

by Jingzi Liu^1,2,3,4,5,*, Peng Liao^1,2,3,4, Junfeng Hu⁵, Hong Zhu^1,2,3,4, Yonglin Wang^1,2,3,4, Yongjun Li^1,2,3,4, Yan Li^6,* and Bin He^1,2,3,4,*

¹ Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, Guizhou, China

² Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, Guizhou, China

³ School of Pharmacy, Guizhou Medical University, Guiyang 550004, Guizhou, China

⁴ National Engineering Research Center of Miao’s Medicines, Guizhou Medical University, Guiyang 550004, Guizhou, China

⁵ School of Pharmacy, Zunyi Medical College, Zunyi 563000, Guizhou, China

⁶ School of Basic Medicine, Guizhou Medical University, Guiyang 550004, Guizhou, China

Molecules 2017, 22(2), 238; https://doi.org/10.3390/molecules22020238 - 16 Feb 2017

Cited by 18 | Viewed by 5258

Abstract

Thiourea derivatives demonstrate potent cytotoxic activity against various leukemias and many tumor cell lines. In our previous study, the combination of thiourea and phosphonate has been proven as an effective strategy for developing antitumor agents. Herein, we synthesized and evaluated a series of [...] Read more.

Thiourea derivatives demonstrate potent cytotoxic activity against various leukemias and many tumor cell lines. In our previous study, the combination of thiourea and phosphonate has been proven as an effective strategy for developing antitumor agents. Herein, we synthesized and evaluated a series of novel chiral dipeptide thioureas containing an α-aminophosphonate moiety as antitumor agents. Finally, we developed novel dipeptide thioureas 11d and 11f that showed comparable inhibition with that of Cisplatin against BGC-823 and A-549 cells, respectively. Full article

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14 pages, 1115 KiB

Open AccessArticle

On-Line Screening, Isolation and Identification of Antioxidant Compounds of Helianthemum ruficomum

by Yasmine Chemam¹, Samir Benayache¹

, Eric Marchioni², Minjie Zhao², Paul Mosset³ and Fadila Benayache^1,*

¹ Unité de Recherche Valorisation des Ressources Naturelles, Molécules Bioactives et Analyses Physicochimiques et Biologiques, Université des Frères Mentouri, Constantine 1, Route d’Aïn El Bey, 25000 Constantine, Algeria

² Chimie Analytique des Molécules Bioactives, Institut Pluridisciplinaire Hubert Curien (UMR 7178 CNRS/UDS), 74 route du Rhin, 67400 Illkirch, France

³ Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Université de Rennes 1, 263 Avenue du Général Leclerc, CS 74205, 35042 Rennes CEDEX, France

Molecules 2017, 22(2), 239; https://doi.org/10.3390/molecules22020239 - 8 Feb 2017

Cited by 34 | Viewed by 6453

Abstract

Many Helianthemum species (Cistaceae) are recognized for their various medicinal virtues. Helianthemum ruficomum is an endemic species to the septentrional Sahara on which no report is available so far. The purpose of this work was to investigate the chemical composition and the radical [...] Read more.

Many Helianthemum species (Cistaceae) are recognized for their various medicinal virtues. Helianthemum ruficomum is an endemic species to the septentrional Sahara on which no report is available so far. The purpose of this work was to investigate the chemical composition and the radical scavenging capacity of this species and its isolated components. Collected from Mougheul (south-west of Algeria), the aerial parts were macerated with 80% EtOH/H₂O, after evaporation, the remaining extract was diluted with H₂O and extracted with petroleum ether, chloroform, ethyl acetate and n-butanol. EtOAc and n-BuOH extracts were evaluated for their free radical scavenging capacity by on-line HPLC-ABTS^•+ assay. The obtained data which were confirmed by TEAC and ORAC assays, allowed guiding the fractionation of these extracts by CC, TLC and reverse phase HPLC. Among the components, 14 were isolated and identified by spectroscopic analyses: protocatechuic acid (1), trans-tiliroside (2), cis-tiliroside (3), astragalin (4), picein (7), vanillic acid 4-O-β-d-glucopyranoside (8), lavandoside (9), 4-hydroxybenzoic acid 4-O-β-d-glucopyranoside (10), nicotiflorin (11), rutin (12), vicenin-2 (13), narcissin (14) and stigmasterol (5) and β-sitosterol (6) as a mixture (71% and 29%, respectively). Compounds 5, 7, 8, 9, 10 and 14 were new for the genus Helianthemum. The antioxidant power of all the isolated compounds was also evaluated by HPLC-ABTS^•+, TEAC and ORAC assays. The results clearly indicated high antioxidant potential of the extracts and tested compounds of this species especially, compounds 1, 4, 8, 9, 10 and 12. Full article

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13 pages, 2045 KiB

Open AccessArticle

Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells

by Chunwa Jiang¹, Muqaddas Masood¹, Azhar Rasul^2,5

, Wei Wei³, Ya Wang¹, Muhammad Ali², Muhammad Mustaqeem⁴, Jiang Li^3,* and Xiaomeng Li^1,*

¹ The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China

² Faculty of Science and Technology, Government College University Faisalabad (GCUF), Faisalabad 38000, Pakistan

³ Dental Hospital, Jilin University, Changchun 130021, China

⁴ Department of Chemistry, University of Sargodha, Sub-campus Bhakkar 30000, Pakistan

⁵ Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, Chemical Biology Department, Wako, Saitama 351-0198, Japan

Molecules 2017, 22(2), 240; https://doi.org/10.3390/molecules22020240 - 7 Feb 2017

Cited by 22 | Viewed by 5879

Abstract

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell [...] Read more.

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 3410 KiB

Open AccessArticle

The Influence of Anion Shape on the Electrical Double Layer Microstructure and Capacitance of Ionic Liquids-Based Supercapacitors by Molecular Simulations

by Ming Chen^1,2, Song Li^1,2,3,* and Guang Feng^1,2

¹ State Key Laboratory of Coal Combustion, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074, China

² Nano Interface Centre for Energy, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074, China

³ Shenzhen Research Institute of Huazhong University of Science and Technology, Shenzhen 518057, China

Molecules 2017, 22(2), 241; https://doi.org/10.3390/molecules22020241 - 16 Feb 2017

Cited by 18 | Viewed by 7210

Abstract

Room-temperature ionic liquids (RTILs) are an emerging class of electrolytes for supercapacitors. In this work, we investigate the effects of different supercapacitor models and anion shape on the electrical double layers (EDLs) of two different RTILs: 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf₂N]) and 1-ethyl-3-methylimidazolium [...] Read more.

Room-temperature ionic liquids (RTILs) are an emerging class of electrolytes for supercapacitors. In this work, we investigate the effects of different supercapacitor models and anion shape on the electrical double layers (EDLs) of two different RTILs: 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf₂N]) and 1-ethyl-3-methylimidazolium 2-(cyano)pyrrolide ([Emim][CNPyr]) by molecular dynamics (MD) simulation. The EDL microstructure is represented by number densities of cations and anions, and the potential drop near neutral and charged electrodes reveal that the supercapacitor model with a single electrode has the same EDL structure as the model with two opposite electrodes. Nevertheless, the employment of the one-electrode model without tuning the bulk density of RTILs is more time-saving in contrast to the two-electrode one. With the one-electrode model, our simulation demonstrated that the shapes of anions significantly imposed effects on the microstructure of EDLs. The EDL differential capacitance vs. potential (C-V) curves of [Emim][CNPyr] electrolyte exhibit higher differential capacitance at positive potentials. The modeling study provides microscopic insight into the EDLs structure of RTILs with different anion shapes. Full article

(This article belongs to the Special Issue Ionic Liquids and Deep Eutectic Solvents for Synthesis, Materials and Energy)

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13 pages, 2699 KiB

Open AccessArticle

Cearoin Induces Autophagy, ERK Activation and Apoptosis via ROS Generation in SH-SY5Y Neuroblastoma Cells

by Tonking Bastola^1,2

, Ren-bo An^1,3, Youn-Chul Kim^1,2, Jaehyo Kim^2,4,* and Jungwon Seo^1,2,*

¹ Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea

² Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea

³ Laboratory of Natural Resources of Changbai Mountain & Functional Molecules Yanbian University, Ministry of Education, Yanji 133002, Jilin, China

⁴ Department of Meridian & Acupoint, College of Korean Medicine, Wonkwang University, Iksan 570-749, Korea

Molecules 2017, 22(2), 242; https://doi.org/10.3390/molecules22020242 - 6 Feb 2017

Cited by 18 | Viewed by 7161

Abstract

Neuroblastomas are the most common solid extracranial tumors in childhood. We investigated the anticancer effect of cearoin isolated from Dalbergia odorifera in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with various doses of cearoin. The viability was measured by MTT assay. DCFDA [...] Read more.

Neuroblastomas are the most common solid extracranial tumors in childhood. We investigated the anticancer effect of cearoin isolated from Dalbergia odorifera in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with various doses of cearoin. The viability was measured by MTT assay. DCFDA fluorescence assay and Griess assay were used for the measurement of intracellular reactive oxygen species (ROS) and nitric oxide (NO), respectively. Western blot analysis was performed to clarify the molecular pathway involved. Cearoin induced cell death in a dose-dependent manner. Cearoin increased the phosporylation of ERK, the conversion of LC3B-I to LC3B-II, decrease in Bcl2 expression, the activation of caspase-3, and the cleavage of PARP, indicating the induction of autophagy and apoptosis. Furthermore, cearoin treatment increased the production of ROS and NO. Co-treatment with the antioxidant N-acetylcysteine completely abolished cearoin-mediated autophagy, ERK activation and apoptosis, suggesting the critical role of ROS in cearoin-induced anticancer effects. Moreover, co-treatment with ERK inhibitor PD98059 partially reversed cearoin-induced cell death, indicating the involvement of ERK in cearoin anticancer effects. These data reveal that cearoin induces autophagy, ERK activation and apoptosis in neuroblastoma SH-SY5Y cells, which is mediated primarily by ROS generation, suggesting its therapeutic application for the treatment of neuroblastomas. Full article

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16 pages, 5946 KiB

Open AccessArticle

Structure and Conformational Properties of d-Glucose/d-Galactose-Binding Protein in Crowded Milieu

by Alexander V. Fonin¹, Sergey A. Silonov^1,2

, Asiya K. Sitdikova^1,3, Irina M. Kuznetsova¹, Vladimir N. Uversky^1,4,*

and Konstantin K. Turoverov^1,3,*

¹ Institute of Cytology of the Russian Academy of Sciences, Laboratory of Structural Dynamics, Stability and Folding of Proteins, Tikhoretsky av. 4, St. Petersburg 197046, Russia

² Saint-Petersburg Technological Institute (Technical University), Moskovsky av. 26, Saint-Petersburg 190013, Russia

³ Department of Biophysics, St. Petersburg State Polytechnical University, Polytechnicheskaya av. 29, St. Petersburg 195251, Russia

⁴ Department of Molecular Medicine and Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA

Molecules 2017, 22(2), 244; https://doi.org/10.3390/molecules22020244 - 6 Feb 2017

Cited by 11 | Viewed by 5572

Abstract

Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted [...] Read more.

Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted compaction of GGBP and lead to the increase in ordering of its structure. Concentrated solutions of PEG-12000 and PEG-4000 caused GGBP aggregation. Although Ficoll-70 and Dextran-70 also promoted increase in the GGBP ordering, the structural outputs were different for different crowders. For example, in comparison with the GGBP in buffer, the intrinsic fluorescence spectrum of this protein was shifted to short-wave region in the presence of PEGs but was red-shifted in the presence of Ficoll-70 and Dextran-70. It was hypothesized that this difference could be due to the specific interaction of GGBP with the sugar-based polymers (Ficoll-70 and Dextran-70), indicating that protein can adopt different conformations in solutions containing molecular crowders of different chemical nature. It was also shown that all tested crowding agents were able to stabilize GGBP structure shifting the GGBP guanidine hydrochloride (GdnHCl)-induced unfolding curves to higher denaturant concentrations, but their stabilization capabilities did not depend on the hydrodynamic dimensions of the polymers molecules. Refolding of GGBP was complicated by protein aggregation in all tested solutions of crowding agents. The lowest yield of refolded protein was achieved in the highly concentrated solutions of PEG-12000. These data support the previous notion that the influence of macromolecular crowders on proteins is rather complex phenomenon that extends beyond the excluded volume effects. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 945 KiB

Open AccessArticle

Intramolecular Hydrogen Bonds in Conformers of Quinine and Quinidine: An HF, MP2 and DFT Study

by Mireille K. Bilonda and Liliana Mammino^*

Department of Chemistry, University of Venda, Thohoyandou 0950, South Africa

Molecules 2017, 22(2), 245; https://doi.org/10.3390/molecules22020245 - 7 Feb 2017

Cited by 14 | Viewed by 8567

Abstract

Quinine is an alkaloid with powerful antimalarial activity, isolated from the bark of Peru’s cinchona trees. Quinidine is an erythro diastereoisomer of quinine also exhibiting antimalarial activity. Conformational studies performed so far had never identified conformers with intramolecular hydrogen bonds (IHB). The current [...] Read more.

Quinine is an alkaloid with powerful antimalarial activity, isolated from the bark of Peru’s cinchona trees. Quinidine is an erythro diastereoisomer of quinine also exhibiting antimalarial activity. Conformational studies performed so far had never identified conformers with intramolecular hydrogen bonds (IHB). The current study shows the possibility of conformers with an IHB between the quinuclidine and quinoline moieties of these molecules. The study was performed at different levels of theory: Hartree Fock (HF) with the 6-31G(d,p) basis set, Density Functional Theory (DFT) with the B3LYP functional and the 6-31+G(d,p) basis set and Møller–Plesset Perturbation Theory (MP2) with the 6-31+G(d,p) basis set, to confirm the results. The results suggest that the stabilising effect of this IHB is weaker or comparable with respect to the stabilising effect of the preferred mutual orientation of the two moieties. Although the IHB-containing conformers may not be the lowest energy ones, their relative energy is sufficiently low for them to be included among the possible ones responsible for the compounds’ antimalarial activity. Full article

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

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10 pages, 2839 KiB

Open AccessCommunication

Poloxamer-Based Thermoreversible Gel for Topical Delivery of Emodin: Influence of P407 and P188 on Solubility of Emodin and Its Application in Cellular Activity Screening

by Eunmi Ban, Mijung Park, Seonghee Jeong, Taekhyun Kwon, Eun-Hee Kim

, Kiwon Jung

and Aeri Kim^*

College of Pharmacy, CHA University, 521 CHA Bio Complex, 335 Pangyo-ro, Bundang-gu, Seongnam 463-400, Korea

Molecules 2017, 22(2), 246; https://doi.org/10.3390/molecules22020246 - 7 Feb 2017

Cited by 77 | Viewed by 9536

Abstract

Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery [...] Read more.

Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407), poloxamer 188 (P188) and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel) and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG) was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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12 pages, 898 KiB

Open AccessArticle

Flavonoid Composition and Antitumor Activity of Bee Bread Collected in Northeast Portugal

by Filipa Sobral¹, Ricardo C. Calhelha¹, Lillian Barros^1,2,*, Montserrat Dueñas³, Andreia Tomás¹, Celestino Santos-Buelga³

, Miguel Vilas-Boas¹

and Isabel C. F. R. Ferreira^1,*

¹ Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, 5300-253 Bragança, Portugal

² Laboratory of Separation and Reaction Engineering—Laboratory of Catalysis and Materials (LSRE-LCM), Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1134, 5301-857 Bragança, Portugal

³ Grupo de Investigación en Polifenoles (GIP-USAL), Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno s/n, 37007 Salamanca, Spain

Molecules 2017, 22(2), 248; https://doi.org/10.3390/molecules22020248 - 7 Feb 2017

Cited by 104 | Viewed by 12755

Abstract

Bee bread (BB) is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives [...] Read more.

Bee bread (BB) is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives located in different apiaries near Bragança, in the northeast region of Portugal, and one BB commercial sample were characterized by high-performance liquid chromatography coupled to a diode array detector and electrospray mass spectrometry (HPLC-DAD-ESI/MS) in terms of phenolic compounds, such as flavonoid glycoside derivatives. Furthermore, the samples were screened, using in vitro assays, against different human tumor cell lines, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HeLa (cervical carcinoma) and HepG2 (hepatocellular carcinoma), and also against non-tumor liver cells (porcine liver cells, PLP2). The main phenolic compounds found were flavonol derivatives, mainly quercetin, kaempferol, myricetin, isorhamnetin and herbacetrin glycoside derivatives. Thirty-two compounds were identified in the six BB samples, presenting BB1 and BB3 with the highest contents (6802 and 6480 µg/g extract, respectively) and the highest number of identified compounds. Two isorhamnetin glycoside derivatives, isrohamnetin-O-hexosyl-O-rutinoside and isorhamnetin-O-pentosyl-hexoside, were the most abundant compounds present in BB1; on the other hand, quercetin-3-O-rhamnoside was the most abundant flavonol in BB3. However, it was not possible to establish a correlation between the flavonoids and the observed low to moderate cytotoxicity (ranging from >400 to 68 µg/mL), in which HeLa and NCI-H460 cell lines were the most susceptible to the inhibition. To the authors’ knowledge, this is the first report characterizing glycosidic flavonoids in BB samples, contributing to the chemical knowledge of this less explored bee product. Full article

(This article belongs to the Collection Bioactive Compounds)

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12 pages, 6878 KiB

Open AccessArticle

Complete Chloroplast Genome of Medicinal Plant Lonicera japonica: Genome Rearrangement, Intron Gain and Loss, and Implications for Phylogenetic Studies

by Liu He¹, Jun Qian¹, Xiwen Li^1,2,*, Zhiying Sun¹, Xiaolan Xu¹ and Shilin Chen^1,2,*

¹ Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

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

Molecules 2017, 22(2), 249; https://doi.org/10.3390/molecules22020249 - 7 Feb 2017

Cited by 102 | Viewed by 9171

Abstract

The complete chloroplast (cp) genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions [...] Read more.

The complete chloroplast (cp) genome of Lonicera japonica, a common ornamental and medicinal plant in North America and East Asia, was sequenced and analyzed. The length of the L. japonica cp genome is 155,078 bp, contains a pair of inverted repeat regions (IRa and IRb), of 23,774 bp each, as well as large (LSC, 88,858 bp) and small (SSC, 18,672 bp) single-copy regions. A total of 129 genes were identified in the cp genome, 16 of which were duplicated within the IR regions. Relative to other plant cp genomes, the L. japonica cp genome had a unique rearrangement between trnI-CAU and trnN-GUU. In L. japonica cpDNA, rps19, rpl2, and rpl23 move to the LSC region, from the IR region. The ycf1 pesudogene in the IR region is lost, and only one copy locates in the SSC region. Comparative cp DNA sequence analyses of L. japonica with other cp genomes reveal that the gene order, and the gene and intron contents, are slightly different. The introns in ycf2 and rps18 genes are found for the first time. Four genes (clpP, petB, petD, and rpl16) lost introns. However, its genome structure, GC content, and codon usage were similar to those of typical angiosperm cp genomes. All preferred synonymous codons were found to use codons ending with A/T. The AT-rich sequences were less abundant in the coding regions than in the non-coding ones. A phylogenetic analysis based on 71 protein-coding genes supported the idea that L. japonica is a sister of the Araliaceae species. This study identified unique characteristics of the L. japonica cp genome that contribute to our understanding of the cpDNA evolution. It offers valuable information for the phylogenetic and specific barcoding of this medicinal plant. Full article

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9 pages, 1404 KiB

Open AccessArticle

Zunyimycins B and C, New Chloroanthrabenzoxocinones Antibiotics against Methicillin-Resistant Staphylococcus aureus and Enterococci from Streptomyces sp. FJS31-2

by Yuhong Lü¹, Meiyun Shao¹, Yinyin Wang¹, Shengyan Qian¹, Miao Wang¹, Yingquan Wang¹, Xiaoqian Li¹, Yuxin Bao¹, Chengmin Deng², Changwu Yue^2,*

, Daishun Liu^2,*, Ning Liu³, Minghao Liu³, Ying Huang^3,*

, Zehui Chen⁴ and Yonglin Hu⁴

¹ Guizhou Key Laboratory of Microbial Resources & Drug Development, Zunyi Medical University, Zunyi 563003, Guizhou, China

² Zunyi Key Laboratory of Genetic Diagnosis & Targeted Drug Therapy, The First People’s Hospital of Zunyi, Zunyi 563003, Guizhou, China

³ State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China

⁴ Department of Clinical Laboratory Medicine, Zunyi Medical University, Zunyi 563003, Guizhou, China

Molecules 2017, 22(2), 251; https://doi.org/10.3390/molecules22020251 - 8 Feb 2017

Cited by 23 | Viewed by 5728

Abstract

This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, [...] Read more.

This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci. Full article

(This article belongs to the Section Medicinal Chemistry)

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9 pages, 1952 KiB

Open AccessArticle

Doxorubicin Conjugated to Glutathione Stabilized Gold Nanoparticles (Au-GSH-Dox) as an Effective Therapeutic Agent for Feline Injection-Site Sarcomas—Chick Embryo Chorioallantoic Membrane Study

by Katarzyna Zabielska-Koczywąs^1,*

, Izabella Dolka¹, Magdalena Król¹, Artur Żbikowski¹, Wiktor Lewandowski²

, Józef Mieczkowski², Michał Wójcik² and Roman Lechowski¹

¹ Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-776 Warsaw, Poland

² Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland

Molecules 2017, 22(2), 253; https://doi.org/10.3390/molecules22020253 - 8 Feb 2017

Cited by 26 | Viewed by 6860

Abstract

Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized [...] Read more.

Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized gold nanoparticles (Au-GSH-Dox) has higher cytotoxic effects than free doxorubicin for feline fibrosarcoma cell lines with high glycoprotein P activity (FFS1, FFS3). The aim of the present study was to assess the effectiveness of intratumoural injection of Au-GSH-Dox on the growth of tumours from the FFS1 and FFS3 cell lines on chick embryo chorioallantoic membrane. This model has been utilized both in human and veterinary medicine for preclinical oncological studies. The influence of intratumoural injections of Au-GSH-Dox, glutathione-stabilized gold nanoparticles and doxorubicin alone on the Ki-67 proliferation marker was also checked. We demonstrated that the volume ratio of tumours from the FFS1 and FFS3 cell lines was significantly (p < 0.01) decreased after a single intratumoural injection of Au-GSH-Dox, which confirms the positive results of in vitro studies and indicates that Au-GSH-Dox may be a potent new therapeutic agent for feline injection-site sarcomas. Full article

(This article belongs to the Special Issue Metal Based Drugs: Opportunities and Challenges)

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12 pages, 2134 KiB

Open AccessCommunication

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products

by Patrycja Miszczyk¹, Dorota Wieczorek², Joanna Gałęzowska³, Błażej Dziuk², Joanna Wietrzyk⁴

and Ewa Chmielewska^1,*

¹ Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, 50-370 Wrocław, Poland

² Faculty of Chemistry, University of Opole, 45-040 Opole, Poland

³ Department of Inorganic Chemistry, Faculty of Pharmacy, Wrocław Medical University, 50-556 Wrocław, Poland

⁴ Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland

Molecules 2017, 22(2), 254; https://doi.org/10.3390/molecules22020254 - 8 Feb 2017

Cited by 8 | Viewed by 9695

Abstract

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that [...] Read more.

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction—namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1) as a major product, along with N-ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid. Full article

(This article belongs to the Special Issue Multicomponent Reaction-Based Synthesis of Bioactive Molecules)

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15 pages, 1108 KiB

Open AccessArticle

Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

by Yosuke Matsubara^1,*, Takashi Matsumoto¹

, Kyoji Sekiguchi¹, Junichi Koseki¹, Atsushi Kaneko¹, Takuji Yamaguchi^1,2, Yumiko Kurihara² and Hiroyuki Kobayashi^2,3

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

² Center for Advanced Kampo Medicine and Clinical Research, Juntendo Graduate School of Medicine, Tokyo 113-8421, Japan

³ Department of Hospital Administration, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan

Molecules 2017, 22(2), 256; https://doi.org/10.3390/molecules22020256 - 8 Feb 2017

Cited by 15 | Viewed by 8578

Abstract

Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to [...] Read more.

Insufficient detoxification and/or overproduction of reactive oxygen species (ROS) induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY) is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs) in plasma. ROS-scavenging and lipid hydroperoxide (LPO) generation assays revealed that gallic acid, 3-O-methylgallic acid, (+)-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases. Full article

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

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15 pages, 1914 KiB

Open AccessArticle

Preparation of “Constrained Geometry” Titanium Complexes of [1,2]Azasilinane Framework for Ethylene/1-Octene Copolymerization

by Seul Lee, Seung Soo Park, Jin Gu Kim, Chung Sol Kim and Bun Yeoul Lee^*

Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea

Molecules 2017, 22(2), 258; https://doi.org/10.3390/molecules22020258 - 9 Feb 2017

Cited by 19 | Viewed by 6447

Abstract

The Me₂Si-bridged ansa-Cp/amido half-metallocene, [Me₂Si(η⁵-Me₄C₅)(N^tBu)]TiCl₂, termed a “constrained-geometry catalyst (CGC)”, is a representative homogeneous Ziegler catalyst. CGC derivatives with the [1,2]azasilinane framework, in which the amide alkyl substituent [...] Read more.

The Me₂Si-bridged ansa-Cp/amido half-metallocene, [Me₂Si(η⁵-Me₄C₅)(N^tBu)]TiCl₂, termed a “constrained-geometry catalyst (CGC)”, is a representative homogeneous Ziegler catalyst. CGC derivatives with the [1,2]azasilinane framework, in which the amide alkyl substituent is joined by the Si-bridge, were prepared, and the catalytic performances of these species was studied. Me₄C₅HSi(Me)(CH₂CH=CH₂)-NH(C(R)(R’)CH=CH₂) (R, R’ = H or methyl; Me₄C₅H = tetramethylcyclopentadienyl) was susceptible to ring closure metathesis (RCM) when treated with Schrock’s Mo-catalyst to afford -Si(Me₄C₅H)(Me)CH₂CH=CHC(R)(R’)NH- containing a six-membered ring framework. Using the precursors and the products of RCM, various CGC derivatives, i.e., [-Si(η⁵-Me₄C₅)(Me)CH₂CH=CHC(R)(H)N-]TiMe₂ (13, R = H; 15, R = Me), [-Si(η⁵-Me₄C₅)(Me)CH₂CH₂CH₂CH₂N]TiMe₂ (14), [(η⁵-Me₄C₅)Si(Me)(CH₂CH=CH₂)NCH₂CH=CH₂]TiMe₂ (16), [(η⁵-Me₄C₅)Si (Me)(CH=CH₂)NCH₂CH=CH₂]TiMe₂ (17), and [(η⁵-Me₄C₅)Si(Me)(CH₂CH₃)NCH₂CH₂CH₃]TiMe₂ (18), were prepared. The catalytic activity of the newly prepared complexes was lower than that of CGC when activated with [Ph₃C][B(C₆F₅)₄]/iBu₃Al. However, the catalytic activity of these species was improved by using tetrabutylaluminoxane ([iBu₂Al]₂O) instead of iBu₃Al and the activity of 14/[Ph₃C][B(C₆F₅)₄]/[iBu₂Al]₂O was comparable to that of CGC/[Ph₃C][B(C₆F₅)₄]/iBu₃Al (4.7 and 5.0 × 10⁶ g/mol-Ti, respectively). Advantageously, the newly prepared complexes produced higher molecular weight poly(ethylene-co-1-octene)s than CGC. Full article

(This article belongs to the Special Issue Organometallic Catalysis for Olefin Polymerization/Oligomerization)

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12 pages, 5184 KiB

Open AccessArticle

Cytotoxicity and Antioxidant Potential of Novel 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole Derivatives

by Adriana Grozav¹, Ioan-Dan Porumb², Luiza Ioana Găină^2,*

, Lorena Filip^3,*

and Daniela Hanganu⁴

¹ Department of Organic Chemistry, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, 8 Victor Babes, Cluj-Napoca RO-400012, Romania

² Research Center on Fundamental and Applied Heterochemistry, Faculty of Chemistry and Chemical Engineering, “Babeş-Bolyai”, University, M. Kogalniceanu 1, Cluj-Napoca RO-400028, Romania

³ Department of Bromatology, Hygiene, Nutrition, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, 8 Victor Babes, Cluj-Napoca RO-400012, Romania

⁴ Department of Pharmacognosy Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, 8 Victor Babes, Cluj-Napoca RO-400012, Romania

Molecules 2017, 22(2), 260; https://doi.org/10.3390/molecules22020260 - 9 Feb 2017

Cited by 57 | Viewed by 6917

Abstract

Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC₅₀ [...] Read more.

Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC₅₀: 11.6 μM (1), and 12.4 μM (3)] and HeLa [IC₅₀: 22.4 μM (1) and 19.4μM (3)] cell lines is reported. Their antioxidant potential was evaluated by spectrophotometric method, using DPPH radical or Fe (TPTZ)³⁺ complex, and EPR spectroscopy, therefore the compounds 1 and 3 showed remarkable antioxidant activity simultaneously with a cytotoxic effect on A2780 and HeLa cell lines. Furthermore, based on theoretical quantum chemical calculation, the present study analyzed the chemoselectivity of the hydrogen extraction from the indolyl-hydrazinil-thiazoles in reaction with free radicals. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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7 pages, 511 KiB

Open AccessArticle

New Furan Derivatives from a Mangrove-Derived Endophytic Fungus Coriolopsis sp. J5

by Liang-Liang Chen, Pei Wang, Hui-Qin Chen, Zhi-Kai Guo, Hao Wang, Hao-Fu Dai^* and Wen-Li Mei^*

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

Molecules 2017, 22(2), 261; https://doi.org/10.3390/molecules22020261 - 9 Feb 2017

Cited by 16 | Viewed by 5119

Abstract

Six new furan derivatives, named 5-(3-methoxy-3-oxopropyl)-furan-2-carboxylic acid (1), 1-(5-(2-hydroxypropanoyl)-furan-2-yl)-pentan-3-one (2), 2-hydroxy-1-(5-(1-hydroxypentyl)-furan-2-yl)-propan-1-one (3), 1-(5-(1,2-dihydroxypropyl)-furan-2-yl)-pentan-1-one (4), 5-(1-hydroxypent-4-en-1-yl)-furan-2-carboxylic acid (5) and 5-(3-hydroxypentyl)-furan-2-carboxylic acid (6), together with two new natural products, named 5-(1-hydroxypentyl)-furan-2-carboxylic acid ( [...] Read more.

Six new furan derivatives, named 5-(3-methoxy-3-oxopropyl)-furan-2-carboxylic acid (1), 1-(5-(2-hydroxypropanoyl)-furan-2-yl)-pentan-3-one (2), 2-hydroxy-1-(5-(1-hydroxypentyl)-furan-2-yl)-propan-1-one (3), 1-(5-(1,2-dihydroxypropyl)-furan-2-yl)-pentan-1-one (4), 5-(1-hydroxypent-4-en-1-yl)-furan-2-carboxylic acid (5) and 5-(3-hydroxypentyl)-furan-2-carboxylic acid (6), together with two new natural products, named 5-(1-hydroxypentyl)-furan-2-carboxylic acid (7) and (E)-5-(2-carboxyvinyl)-furan-2-carboxylic acid (8), were isolated from the solid rice fermentation of endophytic fungus Coriolopsis sp. J5, which was derived from mangrove plant Ceriops tagal. Their structures were unambiguously elucidated based on 1D and 2D NMR spectroscopy, and by HRESIMS measurements, as well as by comparison with the literature. Full article

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10 pages, 3101 KiB

Open AccessArticle

Influence of Weak Base Addition to Hole-Collecting Buffer Layers in Polymer:Fullerene Solar Cells

by Jooyeok Seo¹, Soohyeong Park², Myeonghun Song¹, Jaehoon Jeong¹, Chulyeon Lee¹, Hwajeong Kim^1,3 and Youngkyoo Kim^1,*

¹ Organic Nanoelectronics Laboratory and KNU Institute for Nanophotonics Applications (KINPA), Department of Chemical Engineering, School of Applied Chemical Engineering, Kyungpook National University, Daegu 41566, Korea

² Advanced Composites Materials Technical Center, Toray Advanced Materials Korea, Gumi-Si, Gyeongbook 39422, Korea

³ Priority Research Center, Research Institute of Advanced Energy Technology, Kyungpook National University, Daegu 41566, Korea

Molecules 2017, 22(2), 262; https://doi.org/10.3390/molecules22020262 - 9 Feb 2017

Cited by 1 | Viewed by 4907

Abstract

We report the effect of weak base addition to acidic polymer hole-collecting layers in normal-type polymer:fullerene solar cells. Varying amounts of the weak base aniline (AN) were added to solutions of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The acidity of the aniline-added PEDOT:PSS solutions gradually decreased from [...] Read more.

We report the effect of weak base addition to acidic polymer hole-collecting layers in normal-type polymer:fullerene solar cells. Varying amounts of the weak base aniline (AN) were added to solutions of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The acidity of the aniline-added PEDOT:PSS solutions gradually decreased from pH = 1.74 (AN = 0 mol% ) to pH = 4.24 (AN = 1.8 mol %). The electrical conductivity of the PEDOT:PSS-AN films did not change much with the pH value, while the ratio of conductivity between out-of-plane and in-plane directions was dependent on the pH of solutions. The highest power conversion efficiency (PCE) was obtained at pH = 2.52, even though all devices with the PEDOT:PSS-AN layers exhibited better PCE than those with the pristine PEDOT:PSS layers. Atomic force microscopy investigation revealed that the size of PEDOT:PSS domains became smaller as the pH increased. The stability test for 100 h illumination under one sun condition disclosed that the PCE decay was relatively slower for the devices with the PEDOT:PSS-AN layers than for those with pristine PEDOT:PSS layers. Full article

(This article belongs to the Special Issue Advances in Organic Nanophotonics)

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11 pages, 232 KiB

Open AccessArticle

A Comparative Analysis of the Chemical Composition, Anti-Inflammatory, and Antinociceptive Effects of the Essential Oils from Three Species of Mentha Cultivated in Romania

by Cristina Mogosan¹

, Oliviu Vostinaru^1,*, Radu Oprean², Codruta Heghes³

, Lorena Filip⁴

, Georgeta Balica⁵ and Radu Ioan Moldovan⁶

¹ Department of Pharmacology, Physiology and Physiopathology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania

² Department of Analytical Chemistry, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania

³ Department of Drug Analysis, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania

⁴ Department of Bromatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania

⁵ Department of Pharmaceutical Botany, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400337, Romania

⁶ SC Fares Biovital Laboratories SRL, Orastie 335700, Romania

Molecules 2017, 22(2), 263; https://doi.org/10.3390/molecules22020263 - 10 Feb 2017

Cited by 68 | Viewed by 8288

Abstract

This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint), Mentha spicata L. [...] Read more.

This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint), Mentha spicata L. subsp. crispata (spearmint), and Mentha suaveolens Ehrh. (pineapple mint). Qualitative and quantitative analysis of the essential oils isolated from the selected Mentha species was performed by gas chromatography coupled with mass spectrometry (GC-MS). The anti-inflammatory activity of the essential oils was determined by the rat paw edema test induced by λ-carrageenan. The antinociceptive effect of the essential oils was evaluated by the writhing test in mice, using 1% (v/v) acetic acid solution administered intraperitonealy and by the hot plate test in mice. The results showed a menthol chemotype for M. piperita pallescens, a carvone chemotype for M. spicata, and a piperitenone oxide chemotype for M. suaveolens. The essential oil from M. spicata L. (EOMSP) produced statistically significant and dose-dependent anti-inflammatory and antinociceptive effects. Full article

(This article belongs to the Section Natural Products Chemistry)

14 pages, 1805 KiB

Open AccessArticle

Betulinic Acid-Mediated Apoptosis in Human Prostate Cancer Cells Involves p53 and Nuclear Factor-Kappa B (NF-κB) Pathways

by Eswar Shankar^1,2, Ailin Zhang¹, Daniel Franco¹ and Sanjay Gupta^1,2,3,4,5,*

¹ Department of Urology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA

² The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA

³ Department of Urology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA

⁴ Department of Nutrition, Case Western Reserve University, Cleveland, OH 44106, USA

⁵ Division of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, OH 44106, USA

Molecules 2017, 22(2), 264; https://doi.org/10.3390/molecules22020264 - 10 Feb 2017

Cited by 65 | Viewed by 7591

Abstract

Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network [...] Read more.

Defects in p53 and nuclear factor-kappa B (NF-κB) signaling pathways are frequently observed in the initiation and development of various human malignancies, including prostate cancer. Clinical studies demonstrate higher expression of NF-κB/p65/RelA, NF-κB/p50/RelB, and cRel as well as downregulation of the p53 network in primary prostate cancer specimens and in metastatic tumors. Betulinic acid (BA), is a triterpenoid that has been reported to be an effective inducer of apoptosis through modification of several signaling pathways. Our objective was to investigate the pathways involved in BA-induced apoptosis in human prostate cancer cells. We employed the androgen-responsive LNCaP cells harboring wild-type p53, and androgen-refractory DU145 cells possessing mutated p53 with high constitutive NF-κB activity. Inhibition of cell survival by BA at 10 and 20 µM concentrations occurred as a result of alteration in Bax/Bcl-2 ratio in both cell lines that led to an increased cytochrome C release, caspase activation and poly(ADP)ribose polymerase (PARP) cleavage, leading to apoptosis. BA treatment resulted in stabilization of p53 through increase in phosphorylation at Ser15 in LNCaP cells, but not in DU145 cells, and induction of cyclin kinase inhibitor p21/Waf1 in both cell types. Furthermore, treatment of both prostate cancer cells with BA decreased the phosphorylation of IκB kinase (IKK)α and I-kappa-B-alpha (IκBα) inhibiting the nuclear location of NF-κB/p65 causing cytosolic accumulation and resulting in its decreased nuclear binding. We demonstrate that BA may induce apoptosis by stabilizing p53 and downregulating NF-κB pathway in human prostate cancer cells, irrespective of the androgen association, and therefore can potentially be developed as a molecule of interest in cancer chemoprevention. Full article

(This article belongs to the Special Issue Cancer Chemoprevention)

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14 pages, 1307 KiB

Open AccessArticle

Structure-Antioxidative and Anti-Inflammatory Activity Relationships of Purpurin and Related Anthraquinones in Chemical and Cell Assays

by Woo Nam¹, Sung Phil Kim^2,3, Seok Hyun Nam^1,* and Mendel Friedman^4,*

¹ Department of Biological Science, Ajou University, Suwon 16499, Korea

² Research Institute of Basic Sciences, Ajou University, Suwon 16499, Korea

³ STR Biotech. Ltd., Chuncheon 24232, Korea

⁴ Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, CA 94710, USA

Molecules 2017, 22(2), 265; https://doi.org/10.3390/molecules22020265 - 10 Feb 2017

Cited by 64 | Viewed by 8190

Abstract

Anthraquinone (9,10-anthraquinone) and several hydroxy derivatives, including purpurin (1,2,4-trihydroxyanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), and chrysazin (1,8-dihydroxyanthraquinone), were evaluated for antioxidative and anti-inflammatory activities in chemical assays and mammalian cells (murine macrophage RAW 264.7 cells). Several tests were used to assess their activities: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free [...] Read more.

Anthraquinone (9,10-anthraquinone) and several hydroxy derivatives, including purpurin (1,2,4-trihydroxyanthraquinone), anthrarufin (1,5-dihydroxyanthraquinone), and chrysazin (1,8-dihydroxyanthraquinone), were evaluated for antioxidative and anti-inflammatory activities in chemical assays and mammalian cells (murine macrophage RAW 264.7 cells). Several tests were used to assess their activities: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical; ABTS radical cation; hydrogen peroxide scavenging; reduction of potassium ferricyanide; chelation of ferrous ions; inhibition of lipid peroxidation; inhibition of nitric oxide generation; scavenging of the intracellular hydroxyl radical; expression of NLRP3 polypeptide for inflammasome assembly; and quantitation of proinflammatory cytokine interleukin 1β (IL-1β) for inflammasome activation. The results show that purpurin, from the root of the madder plant (Rubia tinctorum L.), exhibited the highest antioxidative activity in both chemical and cultured cell antioxidant assays. The antioxidative activities of the other three anthraquinones were lower than that of purpurin. In addition, purpurin could down-regulate NLRP3 inflammasome assembly and activation, suggesting that it might protect foods against oxidative damage and prevent in vivo oxidative stress and inflammation. Structure-activity relationships and the significance of the results for food quality and human health are discussed. Full article

(This article belongs to the Special Issue Structure-Activity Relationship of Natural Products)

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16 pages, 1201 KiB

Open AccessArticle

Synthesis of Some New 1,3,4-Thiadiazole, Thiazole and Pyridine Derivatives Containing 1,2,3-Triazole Moiety

by Nadia A. Abdelriheem, Ali M. M. Mohamed and Abdou O. Abdelhamid^*

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

Molecules 2017, 22(2), 268; https://doi.org/10.3390/molecules22020268 - 10 Feb 2017

Cited by 16 | Viewed by 8049

Abstract

In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and [...] Read more.

In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and pyrazolylthioamide to give 1,3-thiazoles derivatives. Subsequently, 3-phenyl2-en-1-one was used to synthesize substituted pyridines and substituted nicotinic acid ester. The latter was converted to its azide compound which was reacted with aromatic amines and phenol to give substituted urea and phenylcarbamate containing 1,2,3-triazole moiety. The newly synthesized compounds were established by elemental analysis, spectral data and alternative synthesis whenever possible. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 2808 KiB

Open AccessArticle

Novel Magnetic Cross-Linked Cellulase Aggregates with a Potential Application in Lignocellulosic Biomass Bioconversion

by Junqi Jia¹, Weiwei Zhang², Zengjie Yang¹, Xianling Yang¹, Na Wang^1,* and Xiaoqi Yu^1,*

¹ Key Laboratory of Green Chemistry Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China

² School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021, China

Molecules 2017, 22(2), 269; https://doi.org/10.3390/molecules22020269 - 10 Feb 2017

Cited by 102 | Viewed by 7516

Abstract

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has [...] Read more.

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has been developed and applied for biomass bioconversion. The crosslinked aggregates could purify and immobilize enzymes in a single operation, and could then be combined with magnetic nanoparticles (MNPs), which provides easy separation of the materials. The immobilized cellulase showed a better activity at a wider temperature range and pH values than that of the free cellulase. After six cycles of consecutive reuse, the immobilized cellulase performed successful magnetic separation and retained 74% of its initial activity when carboxylmethyl cellulose (CMC) was used as the model substrate. Furthermore, the structure and morphology of the immobilized cellulase were studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the immobilized cellulase was shown to hydrolyze bamboo biomass with a yield of 21%, and was re-used in biomass conversion up to four cycles with 38% activity retention, which indicated that the immobilized enzyme has good potential for biomass applications. Full article

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

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9 pages, 2550 KiB

Open AccessArticle

Rapid High Performance Liquid Chromatography Determination and Optimization of Extraction Parameters of the α-Asarone Isolated from Perilla frutescens L.

by Seung Hwan Hwang^1,2,†, Shin Hwa Kwon^3,†, Young-Hee Kang¹, Jae-Yong Lee^3,4 and Soon Sung Lim^1,2,3,*

¹ Department of Food Science and Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

² Institute of Korean Nutrition, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

³ Institute of Natural Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

⁴ Department of Biochemistry, School of Medicine, Hallym University, 1 Hallymdeahak-gil, Chuncheon 24252, Korea

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 270; https://doi.org/10.3390/molecules22020270 - 10 Feb 2017

Cited by 5 | Viewed by 4830

Abstract

Response surface methodology (RSM), based on a central composite design, was used to determine the best liquid-to-raw material ratio (10:3–15 mL/g), extraction time (1–3 h), and ethanol concentration (50%–100%) for maximum content of α-asarone from Perilla frutescens (PF) extract. Experimental values of α-asarone [...] Read more.

Response surface methodology (RSM), based on a central composite design, was used to determine the best liquid-to-raw material ratio (10:3–15 mL/g), extraction time (1–3 h), and ethanol concentration (50%–100%) for maximum content of α-asarone from Perilla frutescens (PF) extract. Experimental values of α-asarone were 9.51–46.36 mg/g; the results fitted a second-order quadratic polynomial model and correlated with the proposed model (R2 > 0.9354). The best conditions were obtained with extraction time of 1.76 h, liquid-to-raw material ratio of 10:13.5 mL/g, and ethanol concentration of 90.37%. Under these conditions, the model predicted extraction content of 40.56 mg/g, while experimental PF content of α-asarone was 43.84 mg/g dried plant. Optimized conditions determined for maximum content of α-asarone were similar to the experimental range. Experimental values agreed with those predicted, thus validating and indicating suitability of both the model and the RSM approach for optimizing extraction conditions. In addition, a reliable, reproducible and accurate method for the quantitative determination of α-asarone by High Performance Liquid Chromatography (HPLC) analysis was developed with limit of detection (LOD), limit of quantitation (LOQ) values of 0.10 and 0.29 µg/mL and excellent linearity (R2 > 0.9999). Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 4220 KiB

Open AccessArticle

A Protein Isolate from Moringa oleifera Leaves Has Hypoglycemic and Antioxidant Effects in Alloxan-Induced Diabetic Mice

by Paulo C. Paula¹, Daniele O. B. Sousa^1,*, Jose T. A. Oliveira¹

, Ana F. U. Carvalho²

, Bella G. T. Alves¹, Mirella L. Pereira¹, Davi F. Farias^1,3, Martonio P. Viana¹, Flavia A. Santos⁴, Talita C. Morais⁴ and Ilka M. Vasconcelos^1,*

¹ Department of Biochemistry and Molecular Biology, Federal University of Ceara, Fortaleza 60440-900, Brazil

² Department of Biology, Federal University of Ceara, Fortaleza 60440-900, Brazil

³ Department of Molecular Biology, Federal University of Paraiba, Joao Pessoa 58051-900, Brazil

⁴ Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza 60430-160, Brazil

Molecules 2017, 22(2), 271; https://doi.org/10.3390/molecules22020271 - 11 Feb 2017

Cited by 67 | Viewed by 11685

Abstract

Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo-LPI, and the hypoglycemic [...] Read more.

Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo-LPI, and the hypoglycemic and antioxidant effects on alloxan-induced diabetic mice were assessed. Mo-LPI was obtained by aqueous extraction, ammonium sulphate precipitation and dialysis. The electrophoresis profile and proteolytic hydrolysis confirmed its protein nature. Mo-LPI showed hemagglutinating activity, cross-reaction with anti-insulin antibodies and precipitation after zinc addition. Single-dose intraperitoneal (i.p.) administration of Mo-LPI (500 mg/kg·bw) reduced the blood glucose level (reductions of 34.3%, 60.9% and 66.4% after 1, 3 and 5 h, respectively). The effect of Mo-LPI was also evidenced in the repeated dose test with a 56.2% reduction in the blood glucose level on the 7th day after i.p. administration. Mo-LPI did not stimulate insulin secretion in diabetic mice. Mo-LPI was also effective in reducing the oxidative stress in diabetic mice by a decrease in malondialdehyde level and increase in catalase activity. Mo-LPI (2500 mg/kg·bw) did not cause acute toxicity to mice. Mo-LPI is a promising alternative or complementary agent to treat diabetes. Full article

(This article belongs to the Special Issue Bioactive Natural Peptides As A Pipeline For Therapeutics)

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12 pages, 812 KiB

Open AccessArticle

Experimental Evidence and In Silico Identification of Tryptophan Decarboxylase in Citrus Genus

by Luigi De Masi^1,*

, Domenico Castaldo^2,3, Domenico Pignone⁴

, Luigi Servillo⁵ and Angelo Facchiano^6,*

¹ Consiglio Nazionale delle Ricerche (CNR), Istituto di Biologia Agroambientale e Forestale (IBAF), via P. Castellino 111, 80131 Napoli, Italy

² Ministero dello Sviluppo Economico (MiSE), via Molise 2, 00187 Roma, Italy

³ Stazione Sperimentale per le Industrie delle Essenze e dei Derivati dagli Agrumi (SSEA), Azienda Speciale della Camera di Commercio di Reggio Calabria, via Gen. Tommasini 2, 89125 Reggio Calabria, Italy

⁴ CNR, Istituto di Bioscienze e Biorisorse (IBBR), via G. Amendola 165/A, 70126 Bari, Italy

⁵ Dipartimento di Biochimica, Biofisica e Patologia Generale, Università degli Studi della Campania "Luigi Vanvitelli", via L. De Crecchio 7, 80138 Napoli, Italy

⁶ CNR, Istituto di Scienze dell’Alimentazione (ISA), via Roma 64, 83100 Avellino, Italy

Molecules 2017, 22(2), 272; https://doi.org/10.3390/molecules22020272 - 11 Feb 2017

Cited by 20 | Viewed by 7018

Abstract

Plant tryptophan decarboxylase (TDC) converts tryptophan into tryptamine, precursor of indolealkylamine alkaloids. The recent finding of tryptamine metabolites in Citrus plants leads to hypothesize the existence of TDC activity in this genus. Here, we report for the first time that, in Citrus x [...] Read more.

Plant tryptophan decarboxylase (TDC) converts tryptophan into tryptamine, precursor of indolealkylamine alkaloids. The recent finding of tryptamine metabolites in Citrus plants leads to hypothesize the existence of TDC activity in this genus. Here, we report for the first time that, in Citrus x limon seedlings, deuterium labeled tryptophan is decarboxylated into tryptamine, from which successively deuterated N,N,N-trimethyltryptamine is formed. These results give an evidence of the occurrence of the TDC activity and the successive methylation pathway of the tryptamine produced from the tryptophan decarboxylation. In addition, with the aim to identify the genetic basis for the presence of TDC, we carried out a sequence similarity search for TDC in the Citrus genomes using as a probe the TDC sequence reported for the plant Catharanthus roseus. We analyzed the genomes of both Citrus clementina and Citrus sinensis, available in public database, and identified putative protein sequences of aromatic l-amino acid decarboxylase. Similarly, 42 aromatic l-amino acid decarboxylase sequences from 23 plant species were extracted from public databases. Potential sequence signatures for functional TDC were then identified. With this research, we propose for the first time a putative protein sequence for TDC in the genus Citrus. Full article

(This article belongs to the Section Natural Products Chemistry)

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9 pages, 1063 KiB

Open AccessArticle

Synthesis and Positive Inotropic Activity of [1,2,4]Triazolo[4,3-a] Quinoxaline Derivatives Bearing Substituted Benzylpiperazine and Benzoylpiperazine Moieties

by Xue-Kun Liu^1,†, Long-Xu Ma^2,†, Zhi-Yu Wei², Xun Cui³, Shi Zhan⁴, Xiu-Mei Yin^2,* and Hu-Ri Piao^2,*

¹ Tonghua Normal University , College of Pharmaceutical and Food Science, Tonghua 134002, China

² Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133000, China

³ College of Medicine, Yanbian University, Yanji 133000, China

⁴ State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130000, China

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 273; https://doi.org/10.3390/molecules22020273 - 11 Feb 2017

Cited by 6 | Viewed by 5510

Abstract

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart [...] Read more.

In an attempt to search for more potent positive inotropic agents, two series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives bearing substituted benzylpiperazine and benzoylpiperazine moieties were synthesized and their positive inotropic activities evaluated by measuring left atrial stroke volume in isolated rabbit heart preparations. Several compounds showed favorable activities compared with the standard drug, milrinone. Compound 6c was the most potent agent, with an increased stroke volume of 12.53% ± 0.30% (milrinone: 2.46% ± 0.07%) at 3 × 10⁻⁵ M. The chronotropic effects of compounds having considerable inotropic effects were also evaluated. Full article

(This article belongs to the Section Medicinal Chemistry)

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16 pages, 2748 KiB

Open AccessArticle

Characterization, Molecular Docking, and In Vitro Dissolution Studies of Solid Dispersions of 20(S)-Protopanaxadiol

by Qi Zhang^1,2,†, Yiqiong Pu^1,†, Bing Wang^1,2,*

, Yuqin Wang³, Tina Tingxia Dong⁴, Tao Guo⁵, Tong Zhang^1,2 and Zhenzhen Cai^6,*

¹ Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

² School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

³ Zhejiang BioAsia Institute of Life Science, No.1938 Xinqun Road, Economic and Technical Development Zone, Pinghu 314200, Zhejiang, China

⁴ Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China

⁵ Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

⁶ Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 274; https://doi.org/10.3390/molecules22020274 - 11 Feb 2017

Cited by 8 | Viewed by 5741

Abstract

In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry [...] Read more.

In this study, we prepared solid dispersions (SDs) of 20(S)-protopanaxadiol (PPD) using a melting-solvent method with different polymers, in order to improve the solubility and dissolution performance of drugs with poor water solubility. The SDs were characterized via differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and molecular docking and dynamics study. DSC and PXRD results indicated that PPD crystallinity in SDs was significantly reduced, and that the majority of PPD is amorphous. No interaction was observed between PPD and polymers on FTIR and NMR spectra. Molecular docking and dynamic calculations indicated that the PPD molecule localized to the interpolated charged surface, rather than within the amorphous polymer chain network, which might help prevent PPD crystallization, consequently enhancing the PPD dispersion in polymers. An in vitro dissolution study revealed that the SDs considerably improved the PPD dissolution performance in distilled water containing 0.35% Tween-80 (T-80). Furthermore, among three PPD-SDs formulations, Poloxamer188 (F68) was the most effective in improving the PPD solubility and was even superior to the mixed polymers. Therefore, the SD prepared with F68 as a hydrophilic polymer carrier might be a promising strategy for improving solubility and in vitro dissolution performance. F68-based SD, containing PPD with a melting-solvent preparation method, can be used as a promising, nontoxic, quick-release, and effective intermediate for other pharmaceutical formulations, in order to achieve a more effective drug delivery. Full article

(This article belongs to the Special Issue Current Trends in Ginseng Research)

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13 pages, 3248 KiB

Open AccessFeature PaperArticle

Anti-Bacterial and Anti-Fungal Activity of Xanthones Obtained via Semi-Synthetic Modification of α-Mangostin from Garcinia mangostana

by Srinivasan Narasimhan¹, Shanmugam Maheshwaran¹, Imad A. Abu-Yousef², Amin F. Majdalawieh², Janarthanam Rethavathi¹, Prince Edwin Das¹ and Palmiro Poltronieri^3,*

¹ Asthagiri Herbal Research Foundation, 162A, Perungudi Industrial Estate, Perungudi, Chennai 600096, India

² Department of Biology, Chemistry and Environmental Sciences, American University of Sharjah, P.O. Box 26666 Sharjah, United Arab Emirates

³ Institute of Sciences of Food Productions, CNR-ISPA, Lecce 73100, Italy

Molecules 2017, 22(2), 275; https://doi.org/10.3390/molecules22020275 - 12 Feb 2017

Cited by 75 | Viewed by 11714

Abstract

The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter [...] Read more.

The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry. Full article

(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

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16 pages, 2349 KiB

Open AccessArticle

Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase

by Seung Ho Baek^1,2, Jong Hyun Lee¹, Chulwon Kim¹, Jeong-Hyeon Ko¹, Seung-Hee Ryu³, Seok-Geun Lee¹

, Woong Mo Yang¹, Jae-Young Um¹, Arunachalam Chinnathambi⁴, Sulaiman Ali Alharbi⁴, Gautam Sethi^4,5,6,* and Kwang Seok Ahn^1,*

¹ College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea

² College of Korean Medicine, Woosuk University, 46 Eoeun-ro, Wansan-gu, Jeonju-si, Jeollabuk-do 54987, Korea

³ Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea

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

⁵ School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6009, Australia

⁶ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore

Molecules 2017, 22(2), 276; https://doi.org/10.3390/molecules22020276 - 13 Feb 2017

Cited by 61 | Viewed by 9591

Abstract

Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer [...] Read more.

Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP) inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells. Full article

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

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16 pages, 3863 KiB

Open AccessArticle

Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer’s Disease

by Joana A. Loureiro¹

, Stephanie Andrade¹, Ana Duarte¹, Ana Rute Neves², Joana Fontes Queiroz², Cláudia Nunes², Emmanuel Sevin³, Laurence Fenart³, Fabien Gosselet³

, Manuel A. N. Coelho¹ and Maria Carmo Pereira^1,*

¹ LEPABE, Department of Chemical Engineering, Faculty of Engineering of the University of Porto, Porto 4500-465, Portugal

² UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy of the University of Porto, Porto 4050-313, Portugal

³ Laboratoire de la barrière hémato-encéphalique (LBHE), University Artois, EA 2465, Lens F-62300, France

Molecules 2017, 22(2), 277; https://doi.org/10.3390/molecules22020277 - 13 Feb 2017

Cited by 290 | Viewed by 18973

Abstract

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to [...] Read more.

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26. Full article

(This article belongs to the Special Issue Improvements for Resveratrol Efficacy)

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14 pages, 3553 KiB

Open AccessArticle

Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats

by Hyun-Jong Cho¹

, Jun-Pil Jee², Ji-Ye Kang³, Dong-Yeop Shin⁴, Han-Gon Choi⁵, Han-Joo Maeng^6,* and Kwan Hyung Cho^3,*

¹ College of Pharmacy, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon 24341, Korea

² College of Pharmacy, Chosun University, 309 Pilmun-daero, Gwangju 61452, Korea

³ College of Pharmacy, Inje University, 197 Inje-ro, Gimhae 50834, Korea

⁴ School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Korea

⁵ College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Ansan 15588, Korea

⁶ College of Pharmacy, Gachon University, 191 Hambakmoei-ro, Yeonsu-gu, Incheon 21936, Korea

Molecules 2017, 22(2), 280; https://doi.org/10.3390/molecules22020280 - 13 Feb 2017

Cited by 22 | Viewed by 9155

Abstract

The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; [...] Read more.

The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; CSD3) at the weight ratio of 1:1 (drug:polymer) using a spray-drying method. The prepared CSDs were characterized by aqueous solubility, differential scanning calorimetry (DSC), powder X-ray diffraction (p-XRD), scanning electron microscopy (SEM), aqueous viscosity, and dissolution test in various media. The oral bioavailability of CSDs was also evaluated in rats and compared with cefdinir powder suspension. The cefdinir in CSDs was amorphous form, as confirmed in the DSC and p-XRD measurements. The developed CSDs commonly resulted in about 9.0-fold higher solubility of cefdinir and a significantly improved dissolution profile in water and at pH 1.2, compared with cefdinir crystalline powder. Importantly, the in vivo oral absorption (represented as AUC_inf) was markedly increased by 4.30-, 6.77- and 3.01-fold for CSD1, CSD2, and CSD3, respectively, compared with cefdinir suspension in rats. The CSD2 prepared with CMC-Na would provide a promising vehicle to enhance dissolution and bioavailability of cefdinir in vivo. Full article

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14 pages, 2302 KiB

Open AccessArticle

Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat

by Nancy Vara-Gama¹, Adriana Valladares-Méndez¹, Gabriel Navarrete-Vazquez¹

, Samuel Estrada-Soto¹

, Luis Manuel. Orozco-Castellanos^2,* and Julio César Rivera-Leyva^1,*

¹ Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, Mexico

² Departamento de Farmacia, Universidad de Guanajuato, 36050 Guanajuato, Guanajuato, Mexico

Molecules 2017, 22(2), 282; https://doi.org/10.3390/molecules22020282 - 14 Feb 2017

Cited by 5 | Viewed by 6060

Abstract

In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in [...] Read more.

In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in duodenum or jejunum. Also, Compound 1 possess two ionic species, first above of pH 4.43 and, the second one is present over pH 6.08. The apparent permeability in everted sac rat intestine model was 8.73 × 10⁻⁶ cm/s in duodenum and 1.62 × 10⁻⁵ cm/s in jejunum, suggesting that Compound 1 has low permeability. Elimination constant after an oral administration of 50 μg/kg in Wistar rat was 1.81 h⁻¹, absorption constant was 3.05 h⁻¹, C_max was 3.57 μg/mL at 0.33 h, AUC_0–α was 956.54 μ/mL·h and distribution volume was 419.4 mL. To IV administration at the same dose, ke was 1.21 h⁻¹, Vd was 399.6 mL and AUC_0–α was 747.81 μ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound 1 is metabolized to Compound 2 probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound 1 would be considered as a prodrug of Compound 2 with potential as an antidiabetic and anti dyslipidemic agent. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 763 KiB

Open AccessArticle

Iron Supply Affects Anthocyanin Content and Related Gene Expression in Berries of Vitis vinifera cv. Cabernet Sauvignon

by Pengbao Shi^1,2, Bing Li¹, Haiju Chen³, Changzheng Song¹, Jiangfei Meng¹, Zhumei Xi^1,4 and Zhenwen Zhang^1,4,*

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

² College of Food Science and Technology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, Hebei, China

³ College of Horticulture Science and Technology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, Hebei, China

⁴ Shaanxi Engineering Research Center for Viti-Viniculture, Yangling 712100, Shaanxi, China

Molecules 2017, 22(2), 283; https://doi.org/10.3390/molecules22020283 - 14 Feb 2017

Cited by 35 | Viewed by 6045

Abstract

Anthocyanins are important compounds for red grape and red wine quality, and can be influenced by supply of nutrients such as nitrogen, phosphorus, potassium, zinc, and iron. The present work aims to gain a better understanding of the effect of iron supply on [...] Read more.

Anthocyanins are important compounds for red grape and red wine quality, and can be influenced by supply of nutrients such as nitrogen, phosphorus, potassium, zinc, and iron. The present work aims to gain a better understanding of the effect of iron supply on anthocyanins concentration in grape berries. To this end, own-rooted four-year-old Cabernet Sauvignon grapevines (Vitis vinifera) were fertigated every three days with 0, 23, 46, 92, and 184 μM iron (Fe) from ferric ethylenediamine di (o-hydroxyphenylacetic) acid (Fe-EDDHA) in a complete nutrient solution. Fe deficiency or excess generally led to higher concentrations of titratable acidity and skin/berry ratio, and to lower reducing sugar content, sugar/acid ratio, pH, berry weight, and concentration of anthocyanins. Most of the individual anthocyanins detected in this study, except cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and cyanidin-3-O-(6-O-coumaryl)-glucoside, in moderate Fe treatment (46 μM) grapes were significantly higher than those of other treatments. Genes encoding chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), leucoanthocyanidin dioxygenase (LDOX), and anthocyanin O-methyltransferase (AOMT) exhibited higher transcript levels in berries from plants cultivated with 46 μM Fe compared to the ones cultivated with other Fe concentrations. We suggest that grape sugar content, anthocyanins content, and transcriptions of genes involved in anthocyanin biosynthesis were correlated with Fe supply concentrations. Full article

(This article belongs to the Section Natural Products Chemistry)

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15 pages, 1467 KiB

Open AccessArticle

Immobilized Trienzymatic System with Enhanced Stabilization for the Biotransformation of Lactose

by Pedro Torres and Francisco Batista-Viera^*

Cátedra de Bioquímica, Departamento de Biociencias, Facultad de Química, Universidad de la República, Gral Flores 2124, 11800 Montevideo, Uruguay

Molecules 2017, 22(2), 284; https://doi.org/10.3390/molecules22020284 - 22 Feb 2017

Cited by 28 | Viewed by 8181

Abstract

The use of ketohexose isomerases is a powerful tool in lactose whey processing, but these enzymes can be very sensitive and expensive. Development of immobilized/stabilized biocatalysts could be a further option to improve the process. In this work, β-galactosidase from Bacillus circulans, [...] Read more.

The use of ketohexose isomerases is a powerful tool in lactose whey processing, but these enzymes can be very sensitive and expensive. Development of immobilized/stabilized biocatalysts could be a further option to improve the process. In this work, β-galactosidase from Bacillus circulans, l-arabinose (d-galactose) isomerase from Enterococcus faecium, and d-xylose (d-glucose) isomerase from Streptomyces rubiginosus were immobilized individually onto Eupergit C and Eupergit C 250 L. Immobilized activity yields were over 90% in all cases. With the purpose of increasing thermostability of derivatives, two post-immobilization treatments were performed: alkaline incubation to favor the formation of additional covalent linkages, and blocking of excess oxirane groups by reacting with glycine. The greatest thermostability was achieved when alkaline incubation was carried out for 24 h, producing l-arabinose isomerase-Eupergit C derivatives with a half-life of 379 h and d-xylose isomerase-Eupergit C derivatives with a half-life of 554 h at 50 °C. Preliminary assays using immobilized and stabilized biocatalysts sequentially to biotransform lactose at pH 7.0 and 50 °C demonstrated improved performances as compared with soluble enzymes. Further improvements in ketohexose productivities were achieved when the three single-immobilizates were incubated simultaneously with lactose in a mono-reactor system. Full article

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

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9 pages, 3709 KiB

Open AccessArticle

High-Yield Production of Levulinic Acid from Pretreated Cow Dung in Dilute Acid Aqueous Solution

by Jialei Su, Feng Shen, Mo Qiu and Xinhua Qi^*

Agro-Environmental Protection Institute, Chinese Academy of Agricultural Sciences, No. 31, Fukang Road, Nankai District, Tianjin 300191, China

Molecules 2017, 22(2), 285; https://doi.org/10.3390/molecules22020285 - 14 Feb 2017

Cited by 19 | Viewed by 7268

Abstract

Agricultural waste cow dung was used as feedstock for the production of a high value–added chemical levulinic acid (LA) in dilute acid aqueous solutions. A high LA yield of 338.9 g/kg was obtained from the pretreated cow dung, which was much higher than [...] Read more.

Agricultural waste cow dung was used as feedstock for the production of a high value–added chemical levulinic acid (LA) in dilute acid aqueous solutions. A high LA yield of 338.9 g/kg was obtained from the pretreated cow dung, which was much higher than that obtained from the crude cow dung (135 g/kg), mainly attributed to the breakage of the lignin fraction in the lignocellulose structure of the cow dung by potassium hydroxide (KOH) pretreatment, and thus enhanced the accessibility of cow dung to the acid sites in the catalytic reaction. Meanwhile, another value-added chemical formic acid could be obtained with a yield of ca. 160 g/kg in the process, implying a total production of ca. 500 g/kg yield for LA and formic acid from the pretreated cow dung with the proposed process. The developed process was shown to be tolerant to high initial substrate loading with a satisfied LA yield. This work provides a promising strategy for the value-increment utilization of liglocellulosic agricultural residues. Full article

(This article belongs to the Special Issue Chemicals from Biomass)

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11 pages, 1667 KiB

Open AccessArticle

Purification and Partial Structural Characterization of a Complement Fixating Polysaccharide from Rhizomes of Ligusticum chuanxiong

by Yuan-Feng Zou¹

, Yu-Ping Fu¹

, Xing-Fu Chen^2,*, Ingvild Austarheim³, Kari Tvete Inngjerdingen³, Chao Huang¹, Lemlem Dugassa Eticha³, Xu Song¹, Lixia Li¹, Bin Feng⁴

, Chang-Liang He¹, Zhong-Qiong Yin¹ and Berit Smestad Paulsen³

¹ Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang 611130, China

² Key Laboratory of Crop Ecophysiology and Farming System in Southwest China, Ministry of Agriculture, College of Agronomy, Sichuan Agricultural University, Wenjiang 611130, China

³ Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern 0316 Oslo, Norway

⁴ Animal Nutrition Institute, Sichuan Agricultural University, Wenjiang 611130, China

Molecules 2017, 22(2), 287; https://doi.org/10.3390/molecules22020287 - 14 Feb 2017

Cited by 29 | Viewed by 6376

Abstract

Rhizome of Ligusticum chuanxiong is an effective medical plant, which has been extensively applied for centuries in migraine and cardiovascular diseases treatment in China. Polysaccharides from this plant have been shown to have interesting bioactivities, but previous studies have only been performed on [...] Read more.

Rhizome of Ligusticum chuanxiong is an effective medical plant, which has been extensively applied for centuries in migraine and cardiovascular diseases treatment in China. Polysaccharides from this plant have been shown to have interesting bioactivities, but previous studies have only been performed on the neutral polysaccharides. In this study, LCP-I-I, a pectic polysaccharide fraction, was obtained from the 100 °C water extracts of L. chuangxiong rhizomes and purified by diethylaminethyl (DEAE) sepharose anion exchange chromatography and gel filtration. Monosaccharide analysis and linkage determination in addition to Fourier transform infrared (FT-IR) spectrometer and Nuclear magnetic resonance (NMR) spectrum, indicated that LCP-I-I is a typical pectic polysaccharide, with homo-galacturonan and rhamnogalacturonan type I regions and arabinogalactan type I and type II (AG-I/AG-II) side chains. LCP-I-I exhibited potent complement fixation activity, ICH₅₀ of 26.3 ± 2.2 µg/mL, and thus has potential as a natural immunomodulator. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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13 pages, 5089 KiB

Open AccessArticle

Preparation of Photoirradiation Molecular Imprinting Polymer for Selective Separation of Branched Cyclodextrins

by Haoran Fan^1,2,3, Jinpeng Wang^1,2,3, Qingran Meng^1,2,3, Xueming Xu^1,2, Tianming Fan⁴ and Zhengyu Jin^1,2,*

¹ The State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China

² School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China

³ Synergetic Innovation Center of Food Safety and Nutrition, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China

⁴ Muyang Group Co., Ltd., Muyang Road, Yangzhou 225127, China

Molecules 2017, 22(2), 288; https://doi.org/10.3390/molecules22020288 - 21 Feb 2017

Cited by 10 | Viewed by 6874

Abstract

In the present study, photoirradiation molecularly imprinted polymer (MIP) with azobenzene was used as a functional monomer for the selective separation of the branched cyclodextrins. The functional monomer 4-methacryloyloxy azobenzene (MAA) and the molecular template 6-O-α-d-maltosyl-β-cyclodextrin (G2-β-CD) were implemented [...] Read more.

In the present study, photoirradiation molecularly imprinted polymer (MIP) with azobenzene was used as a functional monomer for the selective separation of the branched cyclodextrins. The functional monomer 4-methacryloyloxy azobenzene (MAA) and the molecular template 6-O-α-d-maltosyl-β-cyclodextrin (G2-β-CD) were implemented for the molecular imprinting. The core-shell structure of photoirradiation MIP was visualized by the transmission electron microscopy (TEM). With Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA), we identified that G2-β-CD was imprinted into the polymer and removed from the MIP. The binding association constant (K_a) and the maximum number of the binding site (N_max) were 1.72 × 10⁴ M⁻¹ and 7.93 μmol·g⁻¹ MIP, respectively. With alternate irradiation at 365 and 440 nm light, the prepared MIP reversibly released and rebound to the G2-β-CD, which resulted in the nearly zero amount of G2-β-CD in the solution. The HPLC results indicated that the purity of G2-β-CD could reach 90.8% after going through MIP. The main finding of our study was that the photoirradiation of MIP was an easy and effective method for the selective separation of the branched cyclodextrins. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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13 pages, 1263 KiB

Open AccessArticle

Anti-Hyperglycemic Activity of Major Compounds from Calea ternifolia

by Sonia Escandón-Rivera¹

, Araceli Pérez-Vásquez¹, Andrés Navarrete¹

, Mariana Hernández¹, Edelmira Linares², Robert Bye² and Rachel Mata^1,*

¹ Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico

² Instituto de Biología, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico

Molecules 2017, 22(2), 289; https://doi.org/10.3390/molecules22020289 - 14 Feb 2017

Cited by 17 | Viewed by 7998

Abstract

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and [...] Read more.

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of 1, 4, and 5, four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene (3), herniarin (6), scoparone (7), and 4′,7-dimethylapigenin (8). In addition, the structure of calein C (5) was confirmed by X-ray analysis. Pharmacological evaluation of the essential oil of the species (31.6–316.2 mg/kg, p.o.) provoked also an important decrement of blood glucose levels during an OSTT. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and active essential oil obtained by hydrodistillation revealed that chromene 1 was the major component (19.92%); sesquiterpenes represented the highest percentage of the essential oil content (55.67%) and included curcumene (7.10%), spathulenol (12.95%) and caryophyllene oxide (13.0%). A suitable High Performance Liquid Chromatography (HPLC) method for quantifying chromenes 1 and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2) was developed and validated according to standard protocols. Full article

(This article belongs to the Collection Bioactive Compounds)

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11 pages, 435 KiB

Open AccessArticle

Clinical Signs, Staphylococcus and Atopic Eczema-Related Seromarkers

by Kam Lun Hon^1,*

, Kathy Yin Ching Tsang¹, Jeng Sum C. Kung¹, Ting Fan Leung¹, Christopher W. K. Lam² and Chun Kwok Wong^3,4

¹ Department of Pediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

² State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China

³ Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China

⁴ Institute of Chinese Medicine and State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong, China

Molecules 2017, 22(2), 291; https://doi.org/10.3390/molecules22020291 - 14 Feb 2017

Cited by 21 | Viewed by 15008

Abstract

Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), [...] Read more.

Childhood eczema or atopic dermatitis (AD) is a distressing disease associated with pruritus, sleep disturbance, impaired quality of life and Staphylococcus aureus isolation. The pathophysiology of AD is complex and various seromarkers of immunity are involved. We investigated if anti-staphylococcal enterotoxin IgE (anti-SE), selected seromarkers of T regulatory (Treg), T helper (Th) and antigen-presenting cells (APC) are associated with clinical signs of disease severity and quality of life. Disease severity was assessed with the Scoring Atopic Dermatitis (SCORAD) index, and quality of life with the Children’s Dermatology Life Quality Index (CDLQI) in AD patients ≤18 years old. Concentrations of anti-staphylococcus enterotoxin A and B immunoglobulin E (anti-SEA and anti-SEB), selected Treg/Th/APC chemokines, skin hydration and transepidermal water loss (TEWL) were measured in these patients. Forty patients with AD [median (interquartile range) age of 13.1 (7.9) years) were recruited. Backward stepwise linear regression (controlling for age, personal allergic rhinitis and asthma, and other blood markers) showed the serum anti-SEB level was positively associated with S. aureus and S. epidermidis isolations, objective SCORAD, clinical signs and CDLQI. TNF-α (a Th1 cytokine) was positively associated with objective SCORAD (B = 4.935, p = 0.010), TGF-β (a Treg cytokine) negatively with disease extent (B = −0.015, p = 0.001), IL-18 (an APC cytokine) positively with disease extent (B = 0.438, p = 0.001) and with TEWL (B = 0.040, p = 0.010), and IL-23 (an APC cytokine) negatively with disease extent (B = −2.812, p = 0.006) and positively with pruritus (B = 0.387, p = 0.007). Conclusions: Blood levels of anti-SEB, Th1, Treg and APC cytokines are correlated with various clinical signs of AD. AD is a systemic immunologic disease involving Staphylococcus aureus, cellular, humoral, cytokine and chemokine pathophysiology. Full article

(This article belongs to the Special Issue Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday)

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16 pages, 1649 KiB

Open AccessArticle

Purification of Houttuynia cordata Thunb. Essential Oil Using Macroporous Resin Followed by Microemulsion Encapsulation to Improve Its Safety and Antiviral Activity

by Jianmei Pang¹, Wujun Dong¹, Yuhuan Li², Xuejun Xia¹, Zhihua Liu¹, Huazhen Hao¹, Lingmin Jiang³ and Yuling Liu^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, 1 Xiannongtan Street, Beijing 100050, China

² Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

³ Beijing Wehand-Bio Pharmaceutical Company Limited, Beijing 102600, China

Molecules 2017, 22(2), 293; https://doi.org/10.3390/molecules22020293 - 15 Feb 2017

Cited by 30 | Viewed by 9751

Abstract

Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy [...] Read more.

Essential oil extracted from Houttuynia cordata Thunb. (H. cordata) is widely used in traditional Chinese medicine due to its excellent biological activities. However, impurities and deficient preparations of the essential oil limit its safety and effectiveness. Herein, we proposed a strategy to prepare H. cordata essential oil (HEO) safely and effectively by combining the solvent extraction and the macroporous resin purification flexibly, and then encapsulating it using microemulsion. The extraction and purification process were optimized by orthogonal experimental design and adsorption-desorption tests, respectively. The average houttuynin content in pure HEO was then validated at 44.3% ± 2.01%, which presented a great potential for industrial application. Subsequently, pure HEO-loaded microemulsion was prepared by high-pressure homogenization and was then fully characterized. Results showed that the pure HEO-loaded microemulsion was successfully prepared with an average particle size of 179.1 nm and a high encapsulation rate of 94.7%. Furthermore, safety evaluation tests and in vitro antiviral testing indicated that the safety and activity of HEO were significantly improved after purification using D101 resin and were further improved by microemulsion encapsulation. These results demonstrated that the purification of HEO by macroporous resin followed by microemulsion encapsulation would be a promising approach for industrial application of HEO for the antiviral therapies. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 5860 KiB

Open AccessArticle

Exogenous and Endogenous Hydrogen Sulfide Protects Gastric Mucosa against the Formation and Time-Dependent Development of Ischemia/Reperfusion-Induced Acute Lesions Progressing into Deeper Ulcerations

by Marcin Magierowski¹

, Katarzyna Magierowska¹, Magdalena Hubalewska-Mazgaj^1,2, Zbigniew Sliwowski¹, Robert Pajdo¹, Grzegorz Ginter¹, Slawomir Kwiecien¹ and Tomasz Brzozowski^1,*

¹ Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland

² Department of Genetic Research and Nutrigenomics, Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Cracow, Poland

Molecules 2017, 22(2), 295; https://doi.org/10.3390/molecules22020295 - 15 Feb 2017

Cited by 33 | Viewed by 7023

Abstract

Hydrogen sulfide (H₂S) is an endogenous mediator, synthesized from l-cysteine by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3-MST). The mechanism(s) involved in H₂S-gastroprotection against ischemia/reperfusion (I/R) lesions and their time-dependent progression into deeper gastric ulcerations [...] Read more.

Hydrogen sulfide (H₂S) is an endogenous mediator, synthesized from l-cysteine by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3-MST). The mechanism(s) involved in H₂S-gastroprotection against ischemia/reperfusion (I/R) lesions and their time-dependent progression into deeper gastric ulcerations have been little studied. We determined the effect of l-cysteine, H₂S-releasing NaHS or slow H₂S releasing compound GYY4137 on gastric blood flow (GBF) and gastric lesions induced by 30 min of I followed by 3, 6, 24 and 48 h of R. Role of endogenous prostaglandins (PGs), afferent sensory nerves releasing calcitonin gene-related peptide (CGRP), the gastric expression of hypoxia inducible factor (HIF)-1α and anti-oxidative enzymes were examined. Rats with or without capsaicin deactivation of sensory nerves were pretreated i.g. with vehicle, NaHS (18–180 μmol/kg) GYY4137 (90 μmol/kg) or l-cysteine (0.8–80 μmol/kg) alone or in combination with (1) indomethacin (14 μmol/kg i.p.), SC-560 (14 μmol/kg), celecoxib (26 μmol/kg); (2) capsazepine (13 μmol/kg i.p.); and (3) CGRP (2.5 nmol/kg i.p.). The area of I/R-induced gastric lesions and GBF were measured by planimetry and H₂-gas clearance, respectively. Expression of mRNA for CSE, CBS, 3-MST, HIF-1α, glutathione peroxidase (GPx)-1, superoxide dismutase (SOD)-2 and sulfide production in gastric mucosa compromised by I/R were determined by real-time PCR and methylene blue method, respectively. NaHS and l-cysteine dose-dependently attenuated I/R-induced lesions while increasing the GBF, similarly to GYY4137 (90 μmol/kg). Capsaicin denervation and capsazepine but not COX-1 and COX-2 inhibitors reduced NaHS- and l-cysteine-induced protection and hyperemia. NaHS increased mRNA expression for SOD-2 and GPx-1 but not that for HIF-1α. NaHS which increased gastric mucosal sulfide release, prevented further progression of acute I/R injury into deeper gastric ulcers at 6, 24 and 48 h of R. We conclude that H₂S-induced gastroprotection against I/R-injury is due to increase in gastric microcirculation, anti-oxidative properties and afferent sensory nerves activity but independent on endogenous prostaglandins. Full article

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

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17 pages, 3980 KiB

Open AccessArticle

Amorphous-Amorphous Phase Separation in API/Polymer Formulations

by Christian Luebbert, Fabian Huxoll and Gabriele Sadowski^*

TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Str. 70, D-44227 Dortmund, Germany

Molecules 2017, 22(2), 296; https://doi.org/10.3390/molecules22020296 - 15 Feb 2017

Cited by 66 | Viewed by 8986

Abstract

The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior [...] Read more.

The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in polymers has been measured and modeled during the last years, the APS phenomenon is still poorly understood. In this study, the crystallization behavior, APS, and glass-transition temperatures formulations of ibuprofen and felodipine in polymeric PLGA excipients exhibiting different ratios of lactic acid and glycolic acid monomers in the PLGA chain were investigated by means of hot-stage microscopy and DSC. APS and recrystallization was observed in ibuprofen/PLGA formulations, while only recrystallization occurred in felodipine/PLGA formulations. Based on a successful modeling of the crystallization behavior using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), the occurrence of APS was predicted in agreement with experimental findings. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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9 pages, 1765 KiB

Open AccessArticle

Physicochemical Characterization and Biological Activities of the Triterpenic Mixture α,β-Amyrenone

by Rosilene G. S. Ferreira^1,2, Walter F. Silva Júnior³, Valdir F. Veiga Junior⁴

, Ádley A. N. Lima³ and Emerson S. Lima^2,*

¹ Higher Normal School, University of the State of Amazonas, Av. Djalma Batista 69050-010, Brazil

² Laboratory of Biological Activity, Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Av. General Rodrigo Otávio, 69077-000-Manaus-AM, Brazil

³ Department of Pharmacy, Federal University of Rio Grande do Norte, Av. Coronel Gustavo Cordeiro de Farias s/n, 59012-570-Natal-RN, Brazil

⁴ Laboratory of Chemistry of Amazonian Biomolecules, Department of Chemistry, Federal University of Amazonas, Av. General Rodrigo Otávio, Manaus, AM 69077-000, Brazil

Molecules 2017, 22(2), 298; https://doi.org/10.3390/molecules22020298 - 16 Feb 2017

Cited by 20 | Viewed by 5877

Abstract

α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,β-amyrins, obtained as major compounds from the same oleoresins. Using a [...] Read more.

α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,β-amyrins, obtained as major compounds from the same oleoresins. Using a very simple, high yield procedure, and using a readily commercially available mixture of α,β-amyrins as substrate, the binary compound α,β-amyrenone was synthesized and submitted to physico-chemical characterization using different techniques such as high-performance liquid chromatography, nuclear magnetic resonance (¹H and ¹³C), mass spectrometry, scanning electron microscopy, differential scanning calorimetry, thermogravimetry and derivative thermogravimetry, and Fourier transform infrared spectroscopy (FTIR). Biological effects were also evaluated by studying the inhibition of enzymes involved in the carbohydrate and lipid absorption process, such as α-amylase, α-glucosidase, lipase, and their inhibitory concentration values of 50% of activity (IC₅₀) were also determined. α,β-Amyrenone significantly inhibited α-glucosidase (96.5% ± 0.52%) at a concentration of 1.6 g/mL. α,β-Amyrenone, at a concentration of 100 µg/mL, showed an inhibition rate on lipase with an IC₅₀ value of 82.99% ± 1.51%. The substances have thus shown in vitro inhibitory effects on the enzymes lipase, α-glucosidase, and α-amylase. These findings demonstrate the potential of α,β-amyrenone for the development of drugs in the treatment of chronic metabolic diseases. Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 5209 KiB

Open AccessArticle

Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives

by Krzysztof Marciniec^1,*, Bartosz Pawełczak², Małgorzata Latocha³, Leszek Skrzypek¹, Małgorzata Maciążek-Jurczyk²

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, Jagiellońska 4, 41-200 Sosnowiec, Poland

² Department of Physical Pharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland

³ Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland

Molecules 2017, 22(2), 300; https://doi.org/10.3390/molecules22020300 - 16 Feb 2017

Cited by 20 | Viewed by 7948

Abstract

In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) [...] Read more.

In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines. Among these compounds, 4-(3-propynylthio)-7-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline shows significant antiprolierative activity against T47D cells with IC₅₀ values of 0.07 µM. In addition, 2-(3-Propynylthio)-6-[N-methyl-N-(3-propynyl)sulfa-moyl]quinoline and 2-(3-propynylseleno)-6-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC₅₀ values of 0.09 and 0.50 µM, respectively. Furthermore, most of the tested compounds show a weak cytotoxic effect against the normal HFF-1 cell line. Additionally, in order to suggest a mechanism of action for their activity, all compounds are docked into the binding site of two human cytochrome P450 (CYP) isoenzymes. These data indicate that some of the title compounds display significant cytotoxic activity, possibly targeting the CYPs pathways. Full article

(This article belongs to the Special Issue Sulfonamides)

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13 pages, 7930 KiB

Open AccessArticle

Green Microwave-Assisted Combustion Synthesis of Zinc Oxide Nanoparticles with Citrullus colocynthis (L.) Schrad: Characterization and Biomedical Applications

by Susan Azizi^1,*

, Rosfarizan Mohamad^1,2,*

and Mahnaz Mahdavi Shahri³

¹ Department of Bioprocess Technology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

² Laboratory of Biopolymer and Derivatives, Institute of Tropical Forestry and Forest Products, Universiti Putra Malaysia, UPM Serdang, Selangor 43400, Malaysia

³ Department of Chemistry, Shiraz Branch, Islamic Azad University, Shiraz 74731-71987, Iran

Molecules 2017, 22(2), 301; https://doi.org/10.3390/molecules22020301 - 16 Feb 2017

Cited by 88 | Viewed by 8687

Abstract

In this paper, a green microwave-assisted combustion approach to synthesize ZnO-NPs using zinc nitrate and Citrullus colocynthis (L.) Schrad (fruit, seed and pulp) extracts as bio-fuels is reported. The structure, optical, and colloidal properties of the synthesized ZnO-NP samples were studied. Results illustrate [...] Read more.

In this paper, a green microwave-assisted combustion approach to synthesize ZnO-NPs using zinc nitrate and Citrullus colocynthis (L.) Schrad (fruit, seed and pulp) extracts as bio-fuels is reported. The structure, optical, and colloidal properties of the synthesized ZnO-NP samples were studied. Results illustrate that the morphology and particle size of the ZnO samples are different and depend on the bio-fuel. The XRD results revealed that hexagonal wurtzite ZnO-NPs with mean particle size of 27–85 nm were produced by different bio-fuels. The optical band gap was increased from 3.25 to 3.40 eV with the decreasing of particle size. FTIR results showed some differences in the surface structures of the as-synthesized ZnO-NP samples. This led to differences in the zeta potential, hydrodynamic size, and more significantly, antioxidant activity through scavenging of 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals. In in vitro cytotoxicity studies on 3T3 cells, a dose dependent toxicity with non-toxic effect of concentration below 0.26 mg/mL was shown for ZnO-NP samples. Furthermore, the as-synthesized ZnO-NPs inhibited the growth of medically significant pathogenic gram-positive (Bacillus subtilis and Methicillin-resistant Staphylococcus aurous) and gram-negative (Peseudomonas aeruginosa and Escherichia coli) bacteria. This study provides a simple, green and efficient approach to produce ZnO nanoparticles for various applications. Full article

(This article belongs to the Section Green Chemistry)

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12 pages, 1817 KiB

Open AccessArticle

Efficient Catalytic Oxidation of 3-Arylthio- and 3-Cyclohexylthio-lapachone Derivatives to New Sulfonyl Derivatives and Evaluation of Their Antibacterial Activities

by Mariana F. do C. Cardoso^1,2

, Ana T. P. C. Gomes¹, Caroline Dos S. Moreira², Mário M. Q. Simões¹

, Maria G. P. M. S. Neves¹

, David R. Da Rocha², Fernando De C. Da Silva²

, Catarina Moreirinha³

, Adelaide Almeida³

, Vitor F. Ferreira^2,* and José A. S. Cavaleiro^1,*

¹ Department of Chemistry and QOPNA, University of Aveiro, Aveiro 3810-193, Portugal

² Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Niterói 24020-150, RJ, Brazil

³ Department of Biology and CESAM, University of Aveiro, Aveiro 3810-193, Portugal

Molecules 2017, 22(2), 302; https://doi.org/10.3390/molecules22020302 - 16 Feb 2017

Cited by 10 | Viewed by 5703

Abstract

New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III) porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the [...] Read more.

New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III) porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus were evaluated after their incorporation into polyvinylpyrrolidone (PVP) micelles. The obtained results show that the PVP-formulations of the lapachones 4b–g and of the sulfonyl-lapachones 7e and 7g reduced the growth of S. aureus. Full article

(This article belongs to the Special Issue Porphyrins and Phthalocyanines: Synthesis, Properties and Applications)

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13 pages, 988 KiB

Open AccessArticle

Application of the Triazolization Reaction to Afford Dihydroartemisinin Derivatives with Anti-HIV Activity

by Sampad Jana¹, Shabina Iram²

, Joice Thomas¹, Muhammad Qasim Hayat²

, Christophe Pannecouque^3,* and Wim Dehaen^1,*

¹ Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium

² Department of Plant Biotechnology, Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12 Islamabad, Pakistan

³ Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium

Molecules 2017, 22(2), 303; https://doi.org/10.3390/molecules22020303 - 17 Feb 2017

Cited by 34 | Viewed by 7661

Abstract

Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole [...] Read more.

Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole derivatives of dihydroartemisinin were synthesized in a single step. All these newly synthesized compounds were characterized and evaluated for their anti-HIV (Human Immunodeficiency Virus) potential in MT-4 cells. Interestingly; three of the synthesized triazole derivatives of dihydroartemisinin showed activities with half maximal inhibitory concentration (IC₅₀) values ranging from 1.34 to 2.65 µM. Full article

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

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12 pages, 1847 KiB

Open AccessArticle

Phytochemical Study of Tapirira guianensis Leaves Guided by Vasodilatory and Antioxidant Activities

by Amélia M. G. Rodrigues^1,2,3, Denise O. Guimarães³, Tatiana U. P. Konno⁴, Luzineide W. Tinoco⁵, Thiago Barth³, Fernando A. Aguiar^6,7, Norberto P. Lopes⁶

, Ivana C. R. Leal⁸

, Juliana M. Raimundo^2,* and Michelle F. Muzitano^3,*

¹ Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Av. Alberto Lamego, 2000, Parque Califórnia, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil

² Laboratório Integrado de Pesquisa, Universidade Federal do Rio de Janeiro, Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros, Macaé, 27930-560 Rio de Janeiro, Brazil

³ Laboratório de Produtos Bioativos, Universidade Federal do Rio de Janeiro, Campus Macaé, Polo Novo Cavaleiro—IMCT, R. Alcides da Conceição, 159, Novo Cavaleiros, Macaé, 27933-378 Rio de Janeiro, Brazil

⁴ Núcleo de Estudos em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé, Universidade Federal do Rio de Janeiro, Av. São José Barreto, 764—São José do Barreto. Macaé, 27965-045 Rio de Janeiro, Brazil

⁵ Instituto de Pesquisa de Produtos Naturais Walter Mors, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil

⁶ Núcleo de Pesquisa em Produtos Naturais e Sintéticos, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n. 14040-020 Ribeirão Preto, Brazil

⁷ Laboratório de Química, Universidade Federal do Rio de Janeiro—Campus Macaé, Av. Aluízio da Silva Gomes, 50, Novo Cavaleiros. Macaé, 27930-560 Rio de Janeiro, Brazil

⁸ Laboratório de Produtos Naturais e Ensaios Biológicos, Departamento De Produtos Naturais e Alimentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil

Molecules 2017, 22(2), 304; https://doi.org/10.3390/molecules22020304 - 18 Feb 2017

Cited by 6 | Viewed by 5373

Abstract

The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and [...] Read more.

The aim of this research was to perform a phytochemical study of the methanol leaves extract of T. guianensis (MET) guided by vasodilatory and antioxidant activities. The chemical profile of MET and the ethyl acetate fraction (EA fraction) was determined by HPLC-UV-MS and EA fraction guided fractionation by reverse-phase chromatography. The vasorelaxant effects of MET, fractions, sub-fractions and constituents were assessed on rat aorta pre-contracted with phenylephrine. Antioxidant activity was evaluated by using a DPPH assay. The results show that MET-induced vasodilation was dependent on NO/cGMP; and that the PI3K/Akt pathway seems to be the main route involved in eNOS activation. The EA fraction showed greater vasodilatory and antioxidant potency and was submitted to further fractionation. This allowed the isolation and characterization of quercetin, quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside and 1,4,6-tri-O-galloyl-β-d-glucose. Also, galloyl-HHDP-hexoside and myricetin deoxyhexoside were identified by HPLC-UV-MS. These compounds are being described for the first time for T. guianensis. 1,4,6-tri-O-galloyl-β-d-glucose and quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside showed no vasodilatory activity. Quercetin and myricetin glycoside seems to contribute to the MET activity, since they have been reported as vasodilatory flavonoids. MET-induced vasodilation could contribute to the hypotensive effect of T. guianensis previously reported. Full article

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12 pages, 13141 KiB

Open AccessArticle

Adsorptive Desulfurization of Model Gasoline by Using Different Zn Sources Exchanged NaY Zeolites

by Jingwei Rui, Fei Liu, Rijie Wang, Yanfei Lu and Xiaoxia Yang^*

Tianjin Key Laboratory of Applied Catalysis Science and Technology, Department of Catalysis Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300354, China

Molecules 2017, 22(2), 305; https://doi.org/10.3390/molecules22020305 - 17 Feb 2017

Cited by 37 | Viewed by 6549

Abstract

A series of Zn-modified NaY zeolites were prepared by the liquid-phase ion-exchange method with different Zn sources, including Zn(NO₃)₂, Zn(Ac)₂ and ZnSO₄. The samples were tested as adsorbents for removing an organic sulfur compound from a [...] Read more.

A series of Zn-modified NaY zeolites were prepared by the liquid-phase ion-exchange method with different Zn sources, including Zn(NO₃)₂, Zn(Ac)₂ and ZnSO₄. The samples were tested as adsorbents for removing an organic sulfur compound from a model gasoline fuel containing 1000 ppmw sulfur. Zn(Ac)₂-Y exhibited the best performance for the desulfurization of gasoline at ambient conditions. Combined with the adsorbents’ characterization results, the higher adsorption capacity of Zn(Ac)₂-Y is associated with a higher ion-exchange degree. Further, the results demonstrated that the addition of 5 wt % toluene or 1-hexene to the diluted thiophene (TP) solution in cyclohexane caused a large decrease in the removal of TP from the model gasoline fuel. This provides evidence about the competition through the π-complexation between TP and toluene for adsorption on the active sites. The acid-catalyzed alkylation by 1-hexene of TP and the generated complex mixture of bulky alkylthiophenes would adsorb on the surface active sites of the adsorbent and block the pores. The regenerated Zn(Ac)₂-Y adsorbent afforded 84.42% and 66.10% of the initial adsorption capacity after the first two regeneration cycles. Full article

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15 pages, 1738 KiB

Open AccessArticle

Ultrasound-Assisted Extraction and Identification of Natural Antioxidants from the Fruit of Melastoma sanguineum Sims

by Tong Zhou¹, Dong-Ping Xu¹, Sheng-Jun Lin², Ya Li¹

, Jie Zheng¹, Yue Zhou¹, Jiao-Jiao Zhang¹ and Hua-Bin Li^1,3,*

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China

² Zhongshan Center for Disease Control and Prevention, Zhongshan 528403, China

³ South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-Sen University, Guangzhou 510006, China

Molecules 2017, 22(2), 306; https://doi.org/10.3390/molecules22020306 - 18 Feb 2017

Cited by 55 | Viewed by 6821

Abstract

The fruit of Melastoma sanguineum Sims is an edible and sweet wild fruit. In our previous study, the fruit was found to have a strong antioxidant property. In this study, an ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the [...] Read more.

The fruit of Melastoma sanguineum Sims is an edible and sweet wild fruit. In our previous study, the fruit was found to have a strong antioxidant property. In this study, an ultrasound-assisted extraction (UAE) method was developed to extract natural antioxidants from the fruit of Melastoma sanguineum Sims, and a response surface methodology was used to optimize the conditions of UAE to maximize the extraction efficiency. The influence of five independent extraction parameters (ethanol concentration, solvent/material ratio, extracting time, temperature, and ultrasound power) on the extraction efficiency were investigated using a single factor experiment, and then a central composite rotatable design was used to investigate the interaction of three key parameters. The results showed that the optimal extraction conditions were 42.98% ethanol, 28.29 mL/g solvent/material ratio, 34.29 min extracting time, 60 °C temperature, and 600 W ultrasound power. Under these conditions, the Trolox equivalent antioxidant capacity (TEAC) value of the extracts was 1074.61 ± 32.56 μmol Trolox/g dry weight (DW). Compared with conventional maceration (723.27 ± 11.61 μmol Trolox/g DW) and Soxhlet extraction methods (518.37 ± 23.23 μmol Trolox/g DW), the UAE method improved the extraction efficiency, in a shorter period of time. In addition, epicatechin gallate, epicatechin, rutin, epigallocatechin, protocatechuic acid, chlorogenic acid, and quercetin, were identified and quantified in the fruit extracts of Melastoma sanguineum Sims by UPLC-MS/MS. Full article

(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)

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12 pages, 6302 KiB

Open AccessArticle

Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors

by Maria Olivero-Acosta, Wilson Maldonado-Rojas and Jesus Olivero-Verbel^*

Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130015, Colombia

Molecules 2017, 22(2), 308; https://doi.org/10.3390/molecules22020308 - 17 Feb 2017

Cited by 12 | Viewed by 6215

Abstract

Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular [...] Read more.

Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular growth. In this study, in silico molecular protein-ligand docking protocols were performed with AutoDock Vina in order to evaluate the interaction of 800 natural compounds (NPs) from the NatProd Collection (http://www.msdiscovery.com/natprod.html), with four human HER family members: HER1 (PDB: 2ITW), HER2 (PDB: 3PP0), HER3 (PDB: 3LMG) and HER4 (PDB: 2R4B). The best binding affinity values (kcal/mol) for docking pairs were obtained for HER1-podototarin (−10.7), HER2-hecogenin acetate (−11.2), HER3-hesperidin (−11.5) and HER4-theaflavin (−10.7). The reliability of the theoretical calculations was evaluated employing published data on HER inhibition correlated with in silico binding calculations. IC₅₀ values followed a significant linear relationship with the theoretical binding Affinity data for HER1 (R = 0.656, p < 0.0001) and HER2 (R = 0.543, p < 0.0001), but not for HER4 (R = 0.364, p > 0.05). In short, this methodology allowed the identification of several NPs as HER inhibitors, being useful in the discovery and design of more potent and selective anticancer drugs. Full article

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10 pages, 821 KiB

Open AccessArticle

Ent-Abietanoids Isolated from Isodon serra

by Jun Wan^1,2, Hua-Yi Jiang^1,2, Jian-Wei Tang^1,2, Xing-Ren Li^1,2, Xue Du¹, Yan Li¹

, Han-Dong Sun¹ and Jian-Xin Pu^1,*

¹ State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

² Kunming College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100039, China

Molecules 2017, 22(2), 309; https://doi.org/10.3390/molecules22020309 - 17 Feb 2017

Cited by 11 | Viewed by 5371

Abstract

Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins [...] Read more.

Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14β)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC₅₀ = 1.8 μM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480). Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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13 pages, 1136 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel 8-Morpholinoimidazo[1,2-a]pyrazine Derivatives Bearing Phenylpyridine/Phenylpyrimidine-Carboxamides

by Shan Xu¹, Chengyu Sun^1,2,*, Chen Chen¹, Pengwu Zheng¹, Yong Zhou², Hongying Zhou² and Wufu Zhu^1,*

¹ School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China

² Department of Pharmacy, The Affiliated Hospital of Chongqing Three Gorges Medical College, Chongqing 404000, China

Molecules 2017, 22(2), 310; https://doi.org/10.3390/molecules22020310 - 17 Feb 2017

Cited by 10 | Viewed by 4855

Abstract

Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC₅₀ values against three cancer cell lines [...] Read more.

Herein we designed and synthesized three series of novel 8-morpholinoimidazo[1,2-a]pyrazine derivatives bearing phenylpyridine/phenylpyrimidine-carboxamides (compounds 12a–g, 13a–g and 14a–g). All the compounds were evaluated for their IC₅₀ values against three cancer cell lines (A549, PC-3 and MCF-7). Most of the target compounds exhibited moderate cytotoxicity against the three cancer cell lines. Two selected compounds 14b, 14c were further tested for their activity against PI3Kα kinase, and the results indicated that compound 14c showed inhibitory activity against PI3Kα kinase with an IC₅₀ value of 1.25 μM. Structure-activity relationships (SARs) and pharmacological results indicated that the replacement of the thiopyranopyrimidine with an imidazopyrazine was beneficial for the activity and the position of aryl group has a significant influence to the activity of these compounds. The compounds 13a–g in which an aryl group substituted at the C-4 position of the pyridine ring were more active than 12a–g substituted at the C-5 position. Moreover, the cytotoxicity of compounds 14a–g bearing phenylpyrimidine-carboxamides was better than that of the compounds 12a–g, 13a–g bearing phenylpyridine-carboxamides. Furthermore, the substituents on the benzene ring also had a significant impact on the cytotoxicity and the pharmacological results showed that electron donating groups were beneficial to the cytotoxicity. Full article

(This article belongs to the Section Medicinal Chemistry)

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10 pages, 1247 KiB

Open AccessArticle

Comparison of the Anti-Inflammatory Activities of Supercritical Carbon Dioxide versus Ethanol Extracts from Leaves of Perilla frutescens Britt. Radiation Mutant

by Chang Hyun Jin^1,2, Han Chul Park¹, Yangkang So¹, Bomi Nam¹, Sung Nim Han² and Jin-Baek Kim^1,*

¹ Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea

² Department of Food and Nutrition, College of Human Ecology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea

Molecules 2017, 22(2), 311; https://doi.org/10.3390/molecules22020311 - 17 Feb 2017

Cited by 13 | Viewed by 5330

Abstract

In this study, we aimed to compare supercritical carbon dioxide extraction and ethanol extraction for isoegomaketone (IK) content in perilla leaf extracts and to identify the optimal method. We measured the IK concentration using HPLC and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 [...] Read more.

In this study, we aimed to compare supercritical carbon dioxide extraction and ethanol extraction for isoegomaketone (IK) content in perilla leaf extracts and to identify the optimal method. We measured the IK concentration using HPLC and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells from the extracts. The IK concentration was 10-fold higher in perilla leaf extracts by supercritical carbon dioxide extraction (SFE) compared with that in perilla leaf extracts by ethanol extraction (EE). When the extracts were treated in LPS-induced RAW 264.7 cells at 25 μg/mL, the SFE inhibited the expression of inflammatory mediators such as nitric oxide (NO), monocyte chemoattractant protein-1 (MCP-1), interleutkin-6 (IL-6), interferon-β (IFN-β), and inducible nitric oxide synthase (iNOS) to a much greater extent compared with EE. Taken together, supercritical carbon dioxide extraction is considered the optimal process for obtaining high IK content and anti-inflammatory activities in leaf extracts from the P. frutescens Britt. radiation mutant. Full article

(This article belongs to the Special Issue Sub- and Supercritical Fluids and Green Chemistry)

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12 pages, 3477 KiB

Open AccessArticle

Phenolic Acid Profiling, Antioxidant, and Anti-Inflammatory Activities, and miRNA Regulation in the Polyphenols of 16 Blueberry Samples from China

by Xianming Su^1,†, Jian Zhang^2,†, Hongqing Wang¹, Jing Xu¹, Jiuming He¹, Liying Liu¹, Ting Zhang³, 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 Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, China

³ Institute of Medical Information & Library, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 3 Yabao Street, Beijing 100020, China

^† These authors contributed equally to this work.

Molecules 2017, 22(2), 312; https://doi.org/10.3390/molecules22020312 - 18 Feb 2017

Cited by 53 | Viewed by 8200

Abstract

To investigate the anti-atherosclerosis related mechanism of blueberries, the phenolic acids (PAs) content, antioxidant and anti-inflammatory activities, as well as the microRNA (miRNA) regulation of polyphenol fractions in blueberry samples from China were studied. Sixteen batches of blueberries including 14 commercialized cultivars (Reka, [...] Read more.

To investigate the anti-atherosclerosis related mechanism of blueberries, the phenolic acids (PAs) content, antioxidant and anti-inflammatory activities, as well as the microRNA (miRNA) regulation of polyphenol fractions in blueberry samples from China were studied. Sixteen batches of blueberries including 14 commercialized cultivars (Reka, Patriot, Brigitta, Bluecrop, Berkeley, Duke, Darrow, Northland, Northblue, Northcountry, Bluesource, Southgood, O’Neal, and Misty) were used in this study. Seven PAs in the polyphenol fractions from 16 blueberry samples in China were quantified by high performance liquid chromatography/tandem mass spectrometry (HPLC/MS²). The antioxidant activities of blueberry polyphenols were tested by (1,1-diphenyl-2-picrylhydrazyl [DPPH]) assay. The anti-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]) activities of the polyphenol fractions of the blueberries were investigated by using lipopolysaccharide (LPS) induced RAW 264.7 macrophages. The correlation analysis showed that the antioxidant (1,1-diphenyl-2-picrylhydrazyl [DPPH]) and anti-inflammatory (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]) activities of the polyphenol fractions of the blueberries were in accordance with their PA contents. Although the polyphenol-enriched fractions of blueberries could inhibit the microRNAs (miRNAs) (miR-21, miR-146a, and miR-125b) to different extents, no significant contribution from the PAs was observed. The inhibition of these miRNAs could mostly be attributed to the other compounds present in the polyphenol-enriched fraction of the blueberries. This is the first study to evaluate the PAs content, antioxidant and anti-inflammatory activities, and miRNA regulation of Chinese blueberries. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 2216 KiB

Open AccessArticle

Accumulation of Carotenoids and Metabolic Profiling in Different Cultivars of Tagetes Flowers

by Yun Ji Park¹, Soo-Yun Park², Mariadhas Valan Arasu³, Naif Abdullah Al-Dhabi³, Hyung-geun Ahn⁴, Jae Kwang Kim^5,*

and Sang Un Park^1,*

¹ Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea

² National Institute of Agricultural Science, Rural Development Administration, Wanju-gun, Jeollabuk-do 565-851, Korea

³ Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia

⁴ Science & Technology Policy Division, Ministry of Agriculture, Food, and Rural Affairs, Sejong-si 30110, Korea

⁵ Division of Life Sciences and Convergence Research Center for Insect Vectors, Incheon National University, Incheon 406-772, Korea

Molecules 2017, 22(2), 313; https://doi.org/10.3390/molecules22020313 - 18 Feb 2017

Cited by 47 | Viewed by 7972

Abstract

Species of Tagetes, which belong to the family Asteraceae show different characteristics including, bloom size, shape, and color; plant size; and leaf shape. In this study, we determined the differences in primary metabolites and carotenoid yields among six cultivars from two Tagetes [...] Read more.

Species of Tagetes, which belong to the family Asteraceae show different characteristics including, bloom size, shape, and color; plant size; and leaf shape. In this study, we determined the differences in primary metabolites and carotenoid yields among six cultivars from two Tagetes species, T. erecta and T. patula. In total, we detected seven carotenoids in the examined cultivars: violaxanthin, lutein, zeaxanthin, α-carotene, β-carotene, 9-cis-β-carotene, and 13-cis-β-carotene. In all the cultivars, lutein was the most abundant carotenoid. Furthermore, the contents of each carotenoid in flowers varied depending on the cultivar. Principal component analysis (PCA) facilitated metabolic discrimination between Tagetes cultivars, with the exception of Inca Yellow and Discovery Orange. Moreover, PCA and orthogonal projection to latent structure-discriminant analysis (OPLS-DA) results provided a clear discrimination between T. erecta and T. patula. Primary metabolites, including xylose, citric acid, valine, glycine, and galactose were the main components facilitating separation of the species. Positive relationships were apparent between carbon-rich metabolites, including those of the TCA cycle and sugar metabolism, and carotenoids. Full article

(This article belongs to the Section Metabolites)

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12 pages, 1326 KiB

Open AccessArticle

Substitution at the C-3 Position of Catechins Has an Influence on the Binding Affinities against Serum Albumin

by Masaki Ikeda¹, Manabu Ueda-Wakagi², Kaori Hayashibara¹, Rei Kitano¹, Masaya Kawase³, Kunihiro Kaihatsu⁴, Nobuo Kato⁴, Yoshitomo Suhara⁵

, Naomi Osakabe⁵ and Hitoshi Ashida^1,*

¹ Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan

² National Agriculture and Food Research Organization, National Food Research Institute, Tsukuba, Ibaraki 305-8642, Japan

³ Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan

⁴ Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, Osaka 567-0047, Japan

⁵ Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan

Molecules 2017, 22(2), 314; https://doi.org/10.3390/molecules22020314 - 18 Feb 2017

Cited by 14 | Viewed by 6734

Abstract

It is known that catechins interact with the tryptophan (Trp) residue at the drug-binding site of serum albumin. In this study, we used catechin derivatives to investigate which position of the catechin structure strongly influences the binding affinity against bovine serum albumin (BSA) [...] Read more.

It is known that catechins interact with the tryptophan (Trp) residue at the drug-binding site of serum albumin. In this study, we used catechin derivatives to investigate which position of the catechin structure strongly influences the binding affinity against bovine serum albumin (BSA) and human serum albumin (HSA). A docking simulation showed that (−)-epigallocatechin gallate (EGCg) interacted with both Trp residues of BSA (one at drug-binding site I and the other on the molecular surface), mainly by π–π stacking. Fluorescence analysis showed that EGCg and substituted EGCg caused a red shift of the peak wavelength of Trp similarly to warfarin (a drug-binding site I-specific compound), while 3-O-acyl-catechins caused a blue shift. To evaluate the binding affinities, the quenching constants were determined by the Stern–Volmer equation. A gallate ester at the C-3 position increased the quenching constants of the catechins. Against BSA, acyl substitution increased the quenching constant proportionally to the carbon chain lengths of the acyl group, whereas methyl substitution decreased the quenching constant. Against HSA, neither acyl nor methyl substitution affected the quenching constant. In conclusion, substitution at the C-3 position of catechins has an important influence on the binding affinity against serum albumin. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 1486 KiB

Open AccessCommunication

An Easy Approach to Control β-Phase Formation in PFO Films for Optimized Emission Properties

by Qi Zhang^1,†, Lang Chi^1,†

, Gang Hai¹, Yueting Fang¹, Xiangchun Li¹, Ruidong Xia^1,*, Wei Huang² and Erdan Gu³

¹ Key Laboratory for Organic Electronics & Information Displays (KLOEID), Jiangsu-Singapore Joint Research Center for Organic/Bio Electronics & Information Displays, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210046, China

² Jiangsu-Singapore Joint Research Center for Organic/Bio-Electronics & Information Displays, Institute of Advanced Materials (IAM), Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, China

³ Institute of Photonics, University of Strathelyde, 106 Rottenrow, Glasgow, G4 0NW, UK

^† These authors contribute equally to this work.

Molecules 2017, 22(2), 315; https://doi.org/10.3390/molecules22020315 - 18 Feb 2017

Cited by 38 | Viewed by 7127

Abstract

We demonstrate a novel approach to control β-phase content generated in poly(9,9-dioctylfluorene) (PFO) films. A very small amount of paraffin oil was used as the additive to the PFO solution in toluene. The β-phase fraction in the spin-coated PFO films can be modified [...] Read more.

We demonstrate a novel approach to control β-phase content generated in poly(9,9-dioctylfluorene) (PFO) films. A very small amount of paraffin oil was used as the additive to the PFO solution in toluene. The β-phase fraction in the spin-coated PFO films can be modified from 0% to 20% simply by changing the volume percentage of paraffin oil in the mixed solution. Organic light emitting diodes (OLEDs) and amplified spontaneous emission (ASE) study confirmed low β-phase fraction promise better OLEDs device, while high β-phase fraction benefits ASE performance. Full article

(This article belongs to the Special Issue Advances in Organic Nanophotonics)

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12 pages, 4582 KiB

Open AccessArticle

A Study on the Electro-Optical Properties of Thiol-Ene Polymer Dispersed Cholesteric Liquid Crystal (PDChLC) Films

by Yujian Sun^1,6, Yanzi Gao^2,3,*, Le Zhou²

, Jianhua Huang¹, Hua Fang¹, Haipeng Ma², Yi Zhang¹, Jie Yang¹, Ping Song², Cuihong Zhang^2,5,*, Lanying Zhang^2,3,*, Fasheng Li^4,*, Yuzhen Zhao^5,* and Kexuan Li^5,*

¹ Department of Materials Physics and Chemistry, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China

² Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China

³ Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Peking University, Beijing 100871, China

⁴ College of Medical Laboratory, Dalian Medical University, Dalian 116044, Liaoning, China

⁵ Department of Applied Statistics and Science, Xijing University, Xi’an 710123, Shaanxi, China

⁶ Anshan Normal University, Anshan 114005, Liaoning, China

Molecules 2017, 22(2), 317; https://doi.org/10.3390/molecules22020317 - 22 Feb 2017

Cited by 23 | Viewed by 6877

Abstract

In this study, a polymer dispersed cholesteric liquid crystal (PDChLC) film obtained via a one-step fabrication technique based on photopolymerization of a thiol-acrylate reaction system was prepared and characterized for the first time. The effects of the chiral dopant, the influence of thiol [...] Read more.

In this study, a polymer dispersed cholesteric liquid crystal (PDChLC) film obtained via a one-step fabrication technique based on photopolymerization of a thiol-acrylate reaction system was prepared and characterized for the first time. The effects of the chiral dopant, the influence of thiol monomer functionality and content on the morphology and subsequent performance of the PDChLC films were systematically investigated. It was demonstrated that the addition of a small amount of chiral dopant slightly increased the driving voltage, but decreased the off-state transmittance significantly. Furthermore, scanning electron micrographs (SEM) shown that the liquid crystal (LC) droplet size decreased at first and then increased with the increasing amount of thiol monomer functionality, while increasing the thiol content increased the LC droplet size. Correspondingly, the electro-optical switching behavior was directly dependent on LC droplet size. By tuning the raw material composition, PDChLC film with optimized electro-optical performance was prepared. Full article

(This article belongs to the Special Issue Advances in Organic Nanophotonics)

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11 pages, 423 KiB

Open AccessArticle

Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata

by Yoseph Atilaw¹, Sandra Duffy², Matthias Heydenreich³

, Lois Muiva-Mutisya¹, Vicky M. Avery²

, Máté Erdélyi^4,5,*

and Abiy Yenesew^1,*

¹ Department of Chemistry, University of Nairobi, P.O. Box 30197, 00100 Nairobi, Kenya

² Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia

³ Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, Germany

⁴ Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden

⁵ Swedish NMR Centre, University of Gothenburg, SE-405 30 Gothenburg, Sweden

Molecules 2017, 22(2), 318; https://doi.org/10.3390/molecules22020318 - 20 Feb 2017

Cited by 14 | Viewed by 6255

Abstract

In our search for new antiplasmodial agents, the CH₂Cl₂/CH₃OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL [...] Read more.

In our search for new antiplasmodial agents, the CH₂Cl₂/CH₃OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2′,6′-dimethoxy-3′,4′-(2′′,2′′-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2′,6′-dimethoxy-3′,4′-(2′′,2′′-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4′′-ethoxy-3′′-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum. Full article

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15 pages, 1390 KiB

Open AccessArticle

An Efficient Synthesis of Novel Bioactive Thiazolyl-Phthalazinediones under Ultrasound Irradiation

by Fatma S. Elsharabasy^1,2, Sobhi M. Gomha³

, Thoraya A. Farghaly^3,4,* and Heba S. A. Elzahabi⁵

¹ Department of Chemistry of Natural and Microbial Products, National Research Center, Dokki 12622, Egypt

² Collage of Science and Humanities, Sattam bin Abdul Aziz University, Alkharj City 11942, Saudi Arabia

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

⁴ Department of Chemistry, Faculty of Applied Science, UmmAl-Qura University, Makkah Almukkarramah 21514, Saudi Arabia

⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), AlAzhar University, Cairo1 1754, Egypt

Molecules 2017, 22(2), 319; https://doi.org/10.3390/molecules22020319 - 18 Feb 2017

Cited by 16 | Viewed by 6050

Abstract

Novel 2-thiazolylphthalazine derivatives were efficiently synthesized under ultrasound irradiation, resulting in high yields and short reaction times after optimization of the reaction conditions. All prepared compounds were fully characterized using spectroscopic methods. They were screened for their antimicrobial activity against Gram-positive and Gram-negative [...] Read more.

Novel 2-thiazolylphthalazine derivatives were efficiently synthesized under ultrasound irradiation, resulting in high yields and short reaction times after optimization of the reaction conditions. All prepared compounds were fully characterized using spectroscopic methods. They were screened for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as for antifungal activity. The antimicrobial activity profile of the tested compounds showed some promising results. The potent activity of compounds 4d, 7b (117% zone inhibition) and 7c (105% zone inhibition) against Salmonella sp., exceeding that of the reference drug Gentamycin is particularly noteworthy. In general, the newly synthesized thiazolylphthalazine derivatives showed higher antimicrobial activity against the tested Gram-negative bacteria than against Gram-positive bacteria and fungi. Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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15 pages, 1456 KiB

Open AccessArticle

Hydrophilic Dogwood Extracts as Materials for Reducing the Skin Irritation Potential of Body Wash Cosmetics

by Zofia Nizioł-Łukaszewska¹, Paweł Osika¹, Tomasz Wasilewski² and Tomasz Bujak^1,*

¹ Department of Cosmetology, The University of Information Technology and Management in Rzeszow, Kielnarowa 386a, Tyczyn 36-020, Poland

² Department of Chemistry, University of Technology and Humanities in Radom, Chrobrego 27, Radom 26-600, Poland

Molecules 2017, 22(2), 320; https://doi.org/10.3390/molecules22020320 - 19 Feb 2017

Cited by 31 | Viewed by 7938

Abstract

A significant problem related to the use of surfactants in body wash cosmetics is their propensity to trigger skin irritations. Only scarce literature exists on the effect of plant extracts on the skin irritation potential. The present study is an attempt to determine [...] Read more.

A significant problem related to the use of surfactants in body wash cosmetics is their propensity to trigger skin irritations. Only scarce literature exists on the effect of plant extracts on the skin irritation potential. The present study is an attempt to determine the effect of hydrophilic dogwood extracts on the irritant potential of body wash gels. Extractants used in the study were water and mixtures of water with glycerine, water with trimethylglycine (betaine), and water with plant-derived glycol (propanediol). The basic biochemical properties, i.e., the ability to neutralize free radicals, and the content of polyphenols, anthocyanins and flavonoids, were determined. An attempt was undertaken to analyze the impact of the extract added to natural body wash gel formulations on product properties. The skin irritation potential was assessed by determining the zein number and the increase in the pH level of the bovine serum albumin (BSA) solution. The viscosity and foaming ability of the resulting products were evaluated. The studies revealed that an addition of dogwood extract contributes to an improvement in the properties of body wash gels and significantly increases the safety of product use through reducing the skin irritation effect. Full article

(This article belongs to the Special Issue Green Production of Bioactive Natural Products)

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13 pages, 794 KiB

Open AccessArticle

Neoflavonoids as Inhibitors of HIV-1 Replication by Targeting the Tat and NF-κB Pathways

by Dionisio A. Olmedo^1,*, José Luis López-Pérez¹

, Esther Del Olmo¹, Luis M. Bedoya^4,5

, Rocío Sancho², José Alcamí⁴, Eduardo Muñoz², Arturo San Feliciano¹

and Mahabir P. Gupta^3,*

¹ Pharmaceutical Chemistry Area, Department of Pharmaceutical Sciences, University of Salamanca, Faculty of Pharmacy, CIETUS, IBSAL, Campus Miguel de Unamuno, 37007 Salamanca, Spain

² Department of Cellular Biology, Physiology and Immunology, University of Córdoba, Faculty of Medicine Avda de Menendez Pidal s/n, 14004 Córdoba, Spain

³ CIFLORPAN, Center for Pharmacognostic Research on Panamanian Flora, College of Pharmacy, University of Panama, P.O. Box 0824-00172 Panama, Panama

⁴ National Centre of Microbiology, Institute Carlos III, Crt. Majadahonda a Pozuelo, 28220 Majadahonda, Madrid, Spain

⁵ Pharmacology Department, College of Pharmacy, Complutense University. Pz. Ramón Y Cajal s/n, 28040 Madrid, Spain

Molecules 2017, 22(2), 321; https://doi.org/10.3390/molecules22020321 - 19 Feb 2017

Cited by 8 | Viewed by 6418

Abstract

Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR [...] Read more.

Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF-κB and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 μM. The assays of these synthetic 4-phenylchromen-2-ones may aid in the investigation of some aspects of the anti-HIV activity of such compounds and could serve as a scaffold for designing better anti-HIV compounds, which may lead to a potential anti-HIV therapeutic drug. Full article

(This article belongs to the Section Bioorganic Chemistry)

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11 pages, 514 KiB

Open AccessArticle

Simultaneous Quantification of Nine New Furanocoumarins in Angelicae Dahuricae Radix Using Ultra-Fast Liquid Chromatography with Tandem Mass Spectrometry

by Lei Zhang, Wei Wei 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(2), 322; https://doi.org/10.3390/molecules22020322 - 20 Feb 2017

Cited by 14 | Viewed by 6021

Abstract

A series of new furanocoumarins with long-chain hydrophobic groups, namely andafocoumarins A–H and J, have been isolated from the dried roots of Angelica dahurica cv. Hangbaizhi (Angelicae Dahuricae radix) in our previous study, among which andafocoumarins A and B were demonstrated to have [...] Read more.

A series of new furanocoumarins with long-chain hydrophobic groups, namely andafocoumarins A–H and J, have been isolated from the dried roots of Angelica dahurica cv. Hangbaizhi (Angelicae Dahuricae radix) in our previous study, among which andafocoumarins A and B were demonstrated to have better anti-inflammatory activity than the positive controls. In this work, a sensitive, accurate, and efficient ultra-fast liquid chromatography coupled with triple quadrupole mass spectrometer (UFLC-MS/MS) method was developed and validated for simultaneous quantification of above-mentioned nine compounds in four cultivars of Angelicae Dahuricae Radix. Chromatographic separation was performed on a Kinetex 2.6u C18 100 Å column (100 × 2.1 mm, 2.6 µm). The mobile phases were comprised of acetonitrile and water with a flow rate of 0.5 mL/min. Using the established method, all components could be easily separated within 12 min. With the multiple reaction monitor mode, all components were detected in positive electrospray ionization. The method was validated with injection precision, linearity, lower limit of detection, lower limit of quantification, precision, recovery, and stability, respectively. The final results demonstrated that the method was accurate and efficient, which could be used to simultaneously quantify the nine andafocoumarins in Angelicae Dahuricae Radix. The results also indicated that in different batches of Angelicae Dahuricae Radix, some of the andafocoumarins were significantly different in terms of content. Full article

(This article belongs to the Collection Bioactive Compounds)

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14 pages, 2075 KiB

Open AccessArticle

Transcriptomic Analysis of Leaf in Tree Peony Reveals Differentially Expressed Pigments Genes

by Jianrang Luo

, Qianqian Shi, Lixin Niu^* and Yanlong Zhang^*

College of Landscape Architecture and Art, Northwest A & F University, Yangling 712100, Shaanxi, China

Molecules 2017, 22(2), 324; https://doi.org/10.3390/molecules22020324 - 20 Feb 2017

Cited by 34 | Viewed by 7320

Abstract

Tree peony (Paeonia suffruticosa Andrews) is an important traditional flower in China. Besides its beautiful flower, the leaf of tree peony has also good ornamental value owing to its leaf color change in spring. So far, the molecular mechanism of leaf color change [...] Read more.

Tree peony (Paeonia suffruticosa Andrews) is an important traditional flower in China. Besides its beautiful flower, the leaf of tree peony has also good ornamental value owing to its leaf color change in spring. So far, the molecular mechanism of leaf color change in tree peony is unclear. In this study, the pigment level and transcriptome of three different color stages of tree peony leaf were analyzed. The purplish red leaf was rich in anthocyanin, while yellowish green leaf was rich in chlorophyll and carotenoid. Transcriptome analysis revealed that 4302 differentially expressed genes (DEGs) were upregulated, and 4225 were downregulated in the purplish red leaf vs. yellowish green leaf. Among these DEGs, eight genes were predicted to participate in anthocyanin biosynthesis, eight genes were predicted involved in porphyrin and chlorophyll metabolism, and 10 genes were predicted to participate in carotenoid metabolism. In addition, 27 MYBs, 20 bHLHs, 36 WD40 genes were also identified from DEGs. Anthocyanidin synthase (ANS) is the key gene that controls the anthocyanin level in tree peony leaf. Protochlorophyllide oxido-reductase (POR) is the key gene which regulated the chlorophyll content in tree peony leaf. Full article

(This article belongs to the Section Molecular Diversity)

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17 pages, 5545 KiB

Open AccessArticle

Analysis of the Total Biflavonoids Extract from Selaginella doederleinii by HPLC-QTOF-MS and Its In Vitro and In Vivo Anticancer Effects

by Hong Yao¹, Bing Chen¹, Yanyan Zhang¹, Huigen Ou¹, Yuxiang Li¹, Shaoguang Li¹, Peiying Shi^2,* and Xinhua Lin^1,*

¹ Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China

² Department of Traditional Chinese Medicine Resource and Bee Products, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Molecules 2017, 22(2), 325; https://doi.org/10.3390/molecules22020325 - 20 Feb 2017

Cited by 76 | Viewed by 11558

Abstract

Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass [...] Read more.

Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. Four types of biflavonoids from S. doederleinii, including IC3′–IIC8′′, IC3′–IIC6′′, IC3′–IIC3′′′, and C–O linked biflavonoids were examined originally using QTOF MS/MS. The fragmentation behavior of IC3′–IIC3′′′ linked biflavonoids was reported for the first time. A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found from S. doederleinii for the first time. Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 2872 KiB

Open AccessArticle

Synthesis and Structural Evaluation of Organo-Ruthenium Complexes with β-Diketonates

by Matija Uršič, Tanja Lipec, Anton Meden and Iztok Turel^*

Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1001 Ljubljana, Slovenia

Molecules 2017, 22(2), 326; https://doi.org/10.3390/molecules22020326 - 20 Feb 2017

Cited by 19 | Viewed by 6830

Abstract

Four novel ruthenium organometallic complexes: [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-bromophenyl)-1,3-butanedione)Cl] (1), [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-bromophenyl)-1,3-butanedione)pta]PF₆ (2), [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-iodophenyl)-1,3-butanedione)Cl] (3) and [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-iodophenyl)-1,3-butanedione)pta]PF₆ (4) were synthesized and [...] Read more.

Four novel ruthenium organometallic complexes: [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-bromophenyl)-1,3-butanedione)Cl] (1), [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-bromophenyl)-1,3-butanedione)pta]PF₆ (2), [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-iodophenyl)-1,3-butanedione)Cl] (3) and [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-iodophenyl)-1,3-butanedione)pta]PF₆ (4) were synthesized and characterized by elemental analysis, infrared (IR), UV-Vis, NMR and mass spectroscopy and single-crystal X-ray diffraction. The crystal structures and spectroscopic data were compared to the previously published complexes [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-chloro-phenyl)-1,3-butanedione)Cl] (5) and [(η⁶-p-cymene)Ru(4,4,4-trifluoro-1-(4-chlorophenyl)-1,3-butanedione)pta]PF₆ (6). The pairs of complexes 1 and 3 as well as 2 and 4 are isostructural, with the former crystallizing in triclinic P-1 and the latter in monoclinic P2₁/c. The ruthenium(II) ion is found in a pseudo-octahedral “piano-stool” geometry in all compounds. Bond lengths and angles are consistent with other complexes of this type. Complexes 2 and 4 exhibit some moderate dynamic disorder. The lack of hydrogen bonding and major π-π interactions means that most of intramolecular interactions are fairly weak and involve halogen atoms present. This was further confirmed by ¹H-NMR spectra, where a significant difference is observed only on the ligand near the halogen atom, following an expected trend. The combined data show that the difference in any activity depends substantially on the type of the ligand′s substituted halogen atom. Full article

(This article belongs to the Section Organometallic Chemistry)

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11 pages, 3849 KiB

Open AccessArticle

Green Hydroselenation of Aryl Alkynes: Divinyl Selenides as a Precursor of Resveratrol

by Gelson Perin^1,*

, Angelita M. Barcellos¹

, Eduardo Q. Luz¹, Elton L. Borges¹, Raquel G. Jacob¹, Eder J. Lenardão¹

, Luca Sancineto² and Claudio Santi^2,*

¹ Laboratório de Síntese Orgânica Limpa-LASOL-CCQFA, Universidade Federal de Pelotas-UFPel, P.O. Box 354, 96010-900 Pelotas, RS, Brazil

² Department of Pharmaceutical Sciences, Group of Catalysis and Organic Green Chemistry, University of Perugia, Via del Liceo 1, 06100 Perugia, Italy

Molecules 2017, 22(2), 327; https://doi.org/10.3390/molecules22020327 - 20 Feb 2017

Cited by 22 | Viewed by 7323

Abstract

A simple and efficient protocol to prepare divinyl selenides has been developed by the regio- and stereoselective addition of sodium selenide species to aryl alkynes. The nucleophilic species was generates in situ, from the reaction of elemental selenium with NaBH₄, [...] Read more.

A simple and efficient protocol to prepare divinyl selenides has been developed by the regio- and stereoselective addition of sodium selenide species to aryl alkynes. The nucleophilic species was generates in situ, from the reaction of elemental selenium with NaBH₄, utilizing PEG-400 as the solvent. Several divinyl selenides were obtained in moderate to excellent yields with selectivity for the (Z,Z)-isomer by a one-step procedure that was carried out at 60 °C in short reaction times. The methodology was extended to tellurium, giving the desired divinyl tellurides in good yields. Furthermore, the Fe-catalyzed cross-coupling reaction of bis(3,5-dimethoxystyryl) selenide 3f with (4-methoxyphenyl)magnesium bromide 5 afforded resveratrol trimethyl ether 6 in 57% yield. Full article

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

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18 pages, 2243 KiB

Open AccessArticle

Diastereoselective Synthesis of Spirocyclopropanes under Mild Conditions via Formal [2 + 1] Cycloadditions Using 2,3-Dioxo-4-benzylidene-pyrrolidines

by Yi Li, Qing-Zhu Li^*, Li Huang, Hong Liang, Kai-Chuan Yang, Hai-Jun Leng, Yue Liu

, Xu-Dong Shen, Xiao-Jun Gou^* and Jun-Long Li^*

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

Molecules 2017, 22(2), 328; https://doi.org/10.3390/molecules22020328 - 22 Feb 2017

Cited by 12 | Viewed by 7044

Abstract

A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral [...] Read more.

A highly diastereoselective cyclopropanation of cyclic enones with sulfur ylides was developed under catalyst-free conditions, producing multifunctional spirocyclopropanes in generally excellent yields (up to 99% yield and >99:1 d.r.). The asymmetric version of this method was realized by using an easily available chiral sulfur ylide, affording products with moderate to good stereoselectivity. Full article

(This article belongs to the Collection Heterocyclic Compounds)

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14 pages, 1345 KiB

Open AccessArticle

Oxidation of 5-Chloromethylfurfural (CMF) to 2,5-Diformylfuran (DFF)

by Ana I. Vicente¹

, Jaime A. S. Coelho¹, Svilen P. Simeonov^1,2, Hristina I. Lazarova², Margarita D. Popova² and Carlos A. M. Afonso^1,*

¹ Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal

² Institute of Organic Chemistry with Centre of Phytochemistry Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 9, 1113, Sofia, Bulgaria

Molecules 2017, 22(2), 329; https://doi.org/10.3390/molecules22020329 - 20 Feb 2017

Cited by 12 | Viewed by 8413

Abstract

2,5-Diformylfuran (DFF) is an important biorenewable building block, namely for the manufacture of new polymers that may replace existing materials derived from limited fossil fuel resources. The current reported methods for the preparation of DFF are mainly derived from the oxidation of 5-hydroxymethylfurfural [...] Read more.

2,5-Diformylfuran (DFF) is an important biorenewable building block, namely for the manufacture of new polymers that may replace existing materials derived from limited fossil fuel resources. The current reported methods for the preparation of DFF are mainly derived from the oxidation of 5-hydroxymethylfurfural (HMF) and, to a lesser extent, directly from fructose. 5-Chloromethylfurfural (CMF) has been considered an alternative to HMF as an intermediate building block due to its advantages regarding stability, polarity, and availability from glucose and cellulose. The only reported method for the transformation of CMF to DFF is restricted to the use of DMSO as the solvent and oxidant. We envisioned that the transformation could be performed using more attractive conditions. To that end, we explored the oxidation of CMF to DFF by screening several oxidants such as H₂O₂, oxone, and pyridine N-oxide (PNO); different heating methods, namely thermal and microwave irradiation (MWI); and also flow conditions. The combination of PNO (4 equiv.) and Cu(OTf)₂ (0.5 equiv.) in acetonitrile was identified as the best system, which lead to the formation of DFF in 54% yield under MWI for 5 min at 160 °C. Consequently, a range of different heterogeneous copper catalysts were tested, which allowed for catalyst reuse. Similar results were also observed under flow conditions using copper immobilized on silica under thermal heating at 160 °C for a residence time of 2.7 min. Finally, HMF and 5,5′-oxybis(5-methylene-2-furaldehyde) (OBMF) were the only byproducts identified under the reaction conditions studied. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd Iberoamerican Symposium on Organic Chemistry (SIBEAQO-3))

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18 pages, 1910 KiB

Open AccessArticle

Metabolic Profiling and Identification of Shikonins in Root Periderm of Two Invasive Echium spp. Weeds in Australia

by Dominik Skoneczny^1,*, Paul A. Weston¹, Xiaocheng Zhu¹

, Geoff M. Gurr^1,2, Ragan M. Callaway³, Russel A. Barrow⁴ and Leslie A. Weston¹

¹ Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW 2678, Australia

² Institute of Applied Ecology, Fujian Agriculture & Forestry University, Fuzhou 350002, China

³ Division of Biological Science, University of Montana, 32 Campus Dr, Missoula, MT 59812, USA

⁴ Research School of Chemistry, Australian National University, Acton, ACT 2601, Australia

Molecules 2017, 22(2), 330; https://doi.org/10.3390/molecules22020330 - 21 Feb 2017

Cited by 28 | Viewed by 7114

Abstract

Metabolic profiling can be successfully implemented to analyse a living system’s response to environmental conditions by providing critical information on an organism’s physiological state at a particular point in time and allowing for both quantitative and qualitative assessment of a specific subset(s) of [...] Read more.

Metabolic profiling can be successfully implemented to analyse a living system’s response to environmental conditions by providing critical information on an organism’s physiological state at a particular point in time and allowing for both quantitative and qualitative assessment of a specific subset(s) of key metabolites. Shikonins are highly reactive chemicals that affect various cell signalling pathways and possess antifungal, antibacterial and allelopathic activity. Based on previous bioassay results, bioactive shikonins, are likely to play important roles in the regulation of rhizosphere interactions with neighbouring plants, microbes and herbivores. An effective platform allowing for rapid identification and accurate profiling of numerous structurally similar, difficult-to-separate bioactive isohexenylnaphthazarins (shikonins) was developed using UHPLC Q-TOF MS. Root periderm tissues of the invasive Australian weeds Echium plantagineum and its congener E. vulgare were extracted overnight in ethanol for shikonin profiling. Shikonin production was evaluated at seedling, rosette and flowering stages. Five populations of each species were compared for qualitative and quantitative differences in shikonin formation. Each species showed little populational variation in qualitative shikonin production; however, shikonin was considerably low in one population of E. plantagineum from Western New South Wales. Seedlings of all populations produced the bioactive metabolite acetylshikonin and production was upregulated over time. Mature plants of both species produced significantly higher total levels of shikonins and isovalerylshikonin > dimethylacrylshikonin > shikonin > acetylshikonin in mature E. plantagineum. Although qualitative metabolic profiles in both Echium spp. were nearly identical, shikonin abundance in mature plant periderm was approximately 2.5 times higher in perennial E. vulgare extracts in comparison to those of the annual E. plantagineum. These findings contribute to our understanding of the biosynthesis of shikonins in roots of two related invasive plants and their expression in relation to plant phenological stage. Full article

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

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12 pages, 3502 KiB

Open AccessArticle

ZYZ-772 Prevents Cardiomyocyte Injury by Suppressing Nox4-Derived ROS Production and Apoptosis

by Ying Wang¹

, Liangjie Zhong¹, Xinhua Liu¹ and Yi Zhun Zhu^1,2,*

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

² School of Pharmacy, Macao University of Science and Technology, Macao

Molecules 2017, 22(2), 331; https://doi.org/10.3390/molecules22020331 - 21 Feb 2017

Cited by 23 | Viewed by 7782

Abstract

Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a [...] Read more.

Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a novel flavonoid was isolated from Zanthoxylum bungeanum. Its structure was elucidated as Quercetin-3-O-(6′′-O-α-l-rhamnopyransoyl)-β-d-glucopyranoside-7-O-β-d-glucopyranoside (ZYZ-772) for the first time. ZYZ-772 exhibited significant cardio-protective property against CoCl₂ induced H9c2 cardiomyocyte cells injury. In CoCl₂ stimulated cardiomyocyte injury, ZYZ-772 inhibited expression of Nox4, and alleviated ROS overproduction. Importantly, ROS triggered MAPKs phosphorylation and P53 signaling mediated apoptosis were restored by ZYZ-772. Our findings present the first piece of evidence for the therapeutic properties of ZYZ-772 in preventing cardiomyocyte injury, which could be attributed to the suppression of Nox4/MAPKs/P53 axis. This will offer a novel therapeutic strategy for the treatment of cardiac ischemia disease. Full article

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

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13 pages, 3982 KiB

Open AccessArticle

Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.)

by Kun Cheng, Hua Gao, Rong-Rong Wang, Yang Liu, Yu-Xue Hou, Xiao-Hong Liu, Kun Liu and Wei Wang^*

School of Pharmacy, Qingdao University, Qingdao 266021, Shandong, China

Molecules 2017, 22(2), 332; https://doi.org/10.3390/molecules22020332 - 21 Feb 2017

Cited by 17 | Viewed by 7045

Abstract

The objective of this research is to implement extraction and degradation methods for the obtainment of 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters—such as ethanol concentration, solvent/solid ratio, extraction [...] Read more.

The objective of this research is to implement extraction and degradation methods for the obtainment of 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters—such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time—were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction time of 10 min at 70 °C under irradiation power 400W provided optimal extraction conditions. Compared with the conventional extraction techniques, including heat reflux extraction (HRE), Soxhlet extraction (SE), and ultrasonic extraction (UE), MAE produced higher extraction efficiency under a lower extraction time. DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one) saponin can be degraded to structurally stable saponin B by the loss of its DDMP group. The influence of pH and the concentration of potassium hydroxide on transformation efficiency of the target compound was investigated. A solution of 0.25 M potassium hydroxide in 75% aqueous ethanol was suitable for converting the corresponding DDMP saponins of chickpeasaponin B1. The implementation by the combining MAE technique and alkaline hydrolysis method for preparing chickpeasaponin B1 provides a convenient technology for future applications. Full article

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

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13 pages, 2315 KiB

Open AccessArticle

One-Pot Conversion of Epoxidized Soybean Oil (ESO) into Soy-Based Polyurethanes by MoCl₂O₂ Catalysis

by Vincenzo Pantone¹, Cosimo Annese², Caterina Fusco²

, Paola Fini³

, Angelo Nacci^2,4

, Antonella Russo¹ and Lucia D’Accolti^2,4,*

¹ Greenswitch s.r.l., 75013 Ferrandina (MT), Italy

² ICCOM-CNR, SS Bari, Via Orabona 4, 70126 Bari, Italy

³ IPCF-CNR, SS Bari, via E. Orabona 4, 70125 Bari, Italy

⁴ Dipartimento di Chimica, Università di Bari “A. Moro”, Via Orabona 4, 70126 Bari, Italy

Molecules 2017, 22(2), 333; https://doi.org/10.3390/molecules22020333 - 21 Feb 2017

Cited by 23 | Viewed by 8118

Abstract

An innovative and eco-friendly one-pot synthesis of bio-based polyurethanes is proposed via the epoxy-ring opening of epoxidized soybean oil (ESO) with methanol, followed by the reaction of methoxy bio-polyols intermediates with 2,6-tolyl-diisocyanate (TDI). Both synthetic steps, methanolysis and polyurethane linkage formation, are promoted [...] Read more.

An innovative and eco-friendly one-pot synthesis of bio-based polyurethanes is proposed via the epoxy-ring opening of epoxidized soybean oil (ESO) with methanol, followed by the reaction of methoxy bio-polyols intermediates with 2,6-tolyl-diisocyanate (TDI). Both synthetic steps, methanolysis and polyurethane linkage formation, are promoted by a unique catalyst, molybdenum(VI) dichloride dioxide (MoCl₂O₂), which makes this procedure an efficient, cost-effective, and environmentally safer method amenable to industrial scale-up. Full article

(This article belongs to the Section Organic Chemistry)

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8 pages, 851 KiB

Open AccessArticle

New Route Synthesis of Thiadiazoles, Bisthiadiazoles, Thiadiazolotriazines, and Pyrazolothiadiazoles Based on Hydrazonoyl Halides and Dihydrazinylthiadiazole

by Abdelwahed R. Sayed^1,2,* and Shar Saad Al-Shihry¹

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

² Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt

Molecules 2017, 22(2), 336; https://doi.org/10.3390/molecules22020336 - 21 Feb 2017

Cited by 8 | Viewed by 5366

Abstract

Synthesis and characterization of new thiadiazoles, bisthiadiazoles from the reaction of mono- and di-hydrazonoyl halides with various hydrazinecarbodithioate derivatives were studied. Treatment of hydrazonoyl halides with 2,5-dihydrazinyl-1,3,4-thiadiazole afforded new bistriazines containing thiadiazole; we also examined the reaction of 2,5-dihydrazinyl-1,3,4-thiadiazole with active methylene compounds [...] Read more.

Synthesis and characterization of new thiadiazoles, bisthiadiazoles from the reaction of mono- and di-hydrazonoyl halides with various hydrazinecarbodithioate derivatives were studied. Treatment of hydrazonoyl halides with 2,5-dihydrazinyl-1,3,4-thiadiazole afforded new bistriazines containing thiadiazole; we also examined the reaction of 2,5-dihydrazinyl-1,3,4-thiadiazole with active methylene compounds to afford new pyrazoles containing thiadiazole compounds. The new synthesized compounds were identified by elemental analysis and various spectral data (Fourier transform infrared spectroscopy, mass spectrometry, 1H and 13C nuclear magnetic resonance). Full article

(This article belongs to the Special Issue Sulfur-Nitrogen Heteroaromatics)

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13 pages, 16869 KiB

Open AccessArticle

A Photocatalytic Rotating Disc Reactor with TiO₂ Nanowire Arrays Deposited for Industrial Wastewater Treatment

by Fang Li¹, Wai Szeto¹, Haibao Huang^1,2, Jiantao Li^3,* and Dennis Y. C. Leung^1,*

¹ Department of Mechanical Engineering, University of Hong Kong, Hong Kong, China

² School of Environmental Science and Engineering, Sun Yat-sen University, Guangzhou 510000, China

³ Sinopec Fushun Research Institute of Petroleum and Petrochemicals (FRIPP), China Petroleum & Chemical Corporation, Fushun 113006, China

Molecules 2017, 22(2), 337; https://doi.org/10.3390/molecules22020337 - 22 Feb 2017

Cited by 7 | Viewed by 6383

Abstract

A photocatalytic rotating disc reactor (PRD-reactor) with TiO₂ nanowire arrays deposited on a thin Ti plate is fabricated and tested for industrial wastewater treatment. Results indicate that the PRD-reactor shows excellent decolorization capability when tested with methyl orange (>97.5%). Advanced oxidation processes [...] Read more.

A photocatalytic rotating disc reactor (PRD-reactor) with TiO₂ nanowire arrays deposited on a thin Ti plate is fabricated and tested for industrial wastewater treatment. Results indicate that the PRD-reactor shows excellent decolorization capability when tested with methyl orange (>97.5%). Advanced oxidation processes (AOP), including photocatalytic oxidation and photolytic reaction, occurred during the processing. Efficiency of the AOP increases with reduction in light absorption pathlength, which enhanced the photocatalytic reaction, as well as by increasing oxygen exposure of the wastewater thin film due to the rotating disc design. It is found that, with a small dosage of hydrogen peroxide, the mineralization efficiency of industrial biodegraded wastewater can be enhanced, with a superior mineralization of >75% total organic carbon (TOC) removal. This is due to the fact that the TiO₂ photocatalysis and hydrogen peroxide processes generate powerful oxidants (hydroxyl radicals) that can strongly improve photocatalytic oxidation efficiency. Application of this industrial wastewater treatment system is benefited from the TiO₂ nanowire arrays, which can be fabricated by a mild solvothermal method at 80 °C and under atmospheric pressure. Similar morphologies and microstructures are found for the TiO₂ nanowire arrays deposited on a large metal Ti disc, which makes the wastewater treatment process more practical and economical. Full article

(This article belongs to the Special Issue Solar Photocatalysis)

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12 pages, 8965 KiB

Open AccessArticle

Synthesis of Reusable Silica Nanosphere-Supported Pt(IV) Complex for Formation of Disulfide Bonds in Peptides

by Xiaonan Hou, Xiaowei Zhao, Yamei Zhang, Aiying Han, Shuying Huo^* and Shigang Shen^*

College of Chemistry and Environmental Science, Key Laboratory of Analytical Science and Technology of Hebei Province, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, No. 180, Wusi Dong Road, Baoding 071002, China

Molecules 2017, 22(2), 338; https://doi.org/10.3390/molecules22020338 - 22 Feb 2017

Cited by 8 | Viewed by 7076

Abstract

Some peptide-based drugs, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bond. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO₂@TPEA@Pt(IV)); TPEA: N-[3-(trimethoxysilyl)propyl]ethylenediamine) was synthesized via a four-step procedure and was used for the formation [...] Read more.

Some peptide-based drugs, including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bond. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO₂@TPEA@Pt(IV)); TPEA: N-[3-(trimethoxysilyl)propyl]ethylenediamine) was synthesized via a four-step procedure and was used for the formation of intramolecular disulfide bonds in peptides. Transmission electron microscopy (TEM) and chemical mapping results for the Pt(II) intermediates and for SiO₂@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly-distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by X-ray photoelectron spectroscopy (XPS). The Pt(IV) loaded on SiO₂@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-VIS spectrometry. The formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by the use of SiO₂@TPEA@Pt(IV) was investigated, and the relative oxidation yields were determined by high-performance liquid chromatography (HPLC). In addition, peptide 1 (Ac-CPFC-NH₂) was utilized to study the reusability of SiO₂@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO₂@TPEA@Pt(IV) after being used for ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex. Full article

(This article belongs to the Section Organic Chemistry)

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14 pages, 944 KiB

Open AccessArticle

Immobilization of Lipase from Penicillium sp. Section Gracilenta (CBMAI 1583) on Different Hydrophobic Supports: Modulation of Functional Properties

by Daniela F. M. Turati^1,2,3, Wilson G. Morais Júnior²

, César R. F. Terrasan^3,*

, Sonia Moreno-Perez⁴, Benevides C. Pessela², Gloria Fernandez-Lorente², Jose M. Guisan^3,*

and Eleonora C. Carmona¹

¹ Department of Biochemistry and Microbiology, Biosciences Institute, Universidade Estadual Paulista (UNESP), 13506-900 Rio Claro, SP, Brazil

² Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, 28049 Madrid, Spain

³ Instituto de Catálisis y Petroleoquímica (ICP), CSIC-UAM, 28049 Madrid, Spain

⁴ Pharmacy and Biotechnology Department, School of Biomedical Sciences, Universidad Europea, 28670 Madrid, Spain

Molecules 2017, 22(2), 339; https://doi.org/10.3390/molecules22020339 - 22 Feb 2017

Cited by 23 | Viewed by 6530

Abstract

Lipases are promising enzymes that catalyze the hydrolysis of triacylglycerol ester bonds at the oil/water interface. Apart from allowing biocatalyst reuse, immobilization can also affect enzyme structure consequently influencing its activity, selectivity, and stability. The lipase from Penicillium sp. section Gracilenta (CBMAI 1583) [...] Read more.

Lipases are promising enzymes that catalyze the hydrolysis of triacylglycerol ester bonds at the oil/water interface. Apart from allowing biocatalyst reuse, immobilization can also affect enzyme structure consequently influencing its activity, selectivity, and stability. The lipase from Penicillium sp. section Gracilenta (CBMAI 1583) was successfully immobilized on supports bearing butyl, phenyl, octyl, octadecyl, and divinylbenzyl hydrophobic moieties wherein lipases were adsorbed through the highly hydrophobic opened active site. The highest activity in aqueous medium was observed for the enzyme adsorbed on octyl support, with a 150% hyperactivation regarding the soluble enzyme activity, and the highest adsorption strength was verified with the most hydrophobic support (octadecyl Sepabeads), requiring 5% Triton X-100 to desorb the enzyme from the support. Most of the derivatives presented improved properties such as higher stability to pH, temperature, and organic solvents than the covalently immobilized CNBr derivative (prepared under very mild experimental conditions and thus a reference mimicking free-enzyme behavior). A 30.8- and 46.3-fold thermostabilization was achieved in aqueous medium, respectively, by the octyl Sepharose and Toyopearl butyl derivatives at 60 °C, in relation to the CNBr derivative. The octyl- and phenyl-agarose derivatives retained 50% activity after four and seven cycles of p-nitrophenyl palmitate hydrolysis, respectively. Different derivatives exhibited different properties regarding their properties for fish oil hydrolysis in aqueous medium and ethanolysis in anhydrous medium. The most active derivative in ethanolysis of fish oil was the enzyme adsorbed on a surface covered by divinylbenzyl moieties and it was 50-fold more active than the enzyme adsorbed on octadecyl support. Despite having identical mechanisms of immobilization, different hydrophobic supports seem to promote different shapes of the adsorbed open active site of the lipase and hence different functional properties. Full article

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

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12 pages, 6551 KiB

Open AccessArticle

Lycium barbarum L. Polysaccharide (LBP) Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell

by Huizhen Cai^1,*, Xiaohui Yang², Qian Cai³, Binbin Ren³, Hongyan Qiu⁴

and Zhiqing Yao¹

¹ Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medicine University, Yinchuan 750004, Ningxia, China

² Department of Sanitary Chemistry, School of Public Health, Ningxia Medicine University, Yinchuan 750004, Ningxia, China

³ Department of Experimental Center, School of Public Health, Ningxia Medicine University, Yinchuan 750004, Ningxia, China

⁴ Department of Epidemiology and Health Statistics, School of Public Health, Ningxia Medicine University, Yinchuan 750004, Ningxia, China

Molecules 2017, 22(2), 341; https://doi.org/10.3390/molecules22020341 - 22 Feb 2017

Cited by 46 | Viewed by 10035

Abstract

Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we [...] Read more.

Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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17 pages, 2893 KiB

Open AccessArticle

Design, Synthesis and Evaluation of Naphthalimide Derivatives as Potential Anticancer Agents for Hepatocellular Carcinoma

by Chaochao Ge^1,2, Liping Chang², Ying Zhao¹, Congcong Chang², Xiaojuan Xu¹, Haoying He¹, Yuxia Wang^3,*

, Fujun Dai^2,*, Songqiang Xie^4,* and Chaojie Wang²

¹ Pharmaceutical College, Henan University, Kaifeng 475001, China

² Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475001, China

³ College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475001, China

⁴ Institute of Chemical Biology, Henan University, Kaifeng 475001, China

Molecules 2017, 22(2), 342; https://doi.org/10.3390/molecules22020342 - 22 Feb 2017

Cited by 23 | Viewed by 7161

Abstract

Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed [...] Read more.

Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation. 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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Jump to: Editorial, Research, Other

29 pages, 2980 KiB

Open AccessReview

Microbial Contribution to Wine Aroma and Its Intended Use for Wine Quality Improvement

by Ignacio Belda¹, Javier Ruiz¹, Adelaida Esteban-Fernández², Eva Navascués³, Domingo Marquina¹, Antonio Santos^1,* and M. Victoria Moreno-Arribas^2,*

¹ Department of Microbiology, Biology Faculty, Complutense University of Madrid, 28040 Madrid, Spain

² CIAL-Institute of Food Science Research (CSIC-UAM), Dpt. Food Biotechnology and Microbiology, 28049 Madrid, Spain

³ Department of Food Technology, Escuela Técnica Superior de Ingenieros Agrónomos, Polytechnic University of Madrid, 28040 Madrid, Spain

Molecules 2017, 22(2), 189; https://doi.org/10.3390/molecules22020189 - 24 Jan 2017

Cited by 270 | Viewed by 21448

Abstract

Wine is a complex matrix that includes components with different chemical natures, the volatile compounds being responsible for wine aroma quality. The microbial ecosystem of grapes and wine, including Saccharomyces and non-Saccharomyces yeasts, as well as lactic acid bacteria, is considered by [...] Read more.

Wine is a complex matrix that includes components with different chemical natures, the volatile compounds being responsible for wine aroma quality. The microbial ecosystem of grapes and wine, including Saccharomyces and non-Saccharomyces yeasts, as well as lactic acid bacteria, is considered by winemakers and oenologists as a decisive factor influencing wine aroma and consumer’s preferences. The challenges and opportunities emanating from the contribution of wine microbiome to the production of high quality wines are astounding. This review focuses on the current knowledge about the impact of microorganisms in wine aroma and flavour, and the biochemical reactions and pathways in which they participate, therefore contributing to both the quality and acceptability of wine. In this context, an overview of genetic and transcriptional studies to explain and interpret these effects is included, and new directions are proposed. It also considers the contribution of human oral microbiota to wine aroma conversion and perception during wine consumption. The potential use of wine yeasts and lactic acid bacteria as biological tools to enhance wine quality and the advent of promising advice allowed by pioneering -omics technologies on wine research are also discussed. Full article

(This article belongs to the Collection Recent Advances in Flavors and Fragrances)

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16 pages, 1461 KiB

Open AccessReview

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

by Alessandro Federico^*

, Marcello Dallio

and Carmelina Loguercio

Department of Clinical and Experimental Medicine, Second University of Naples, 80131 Naples, Italy

Molecules 2017, 22(2), 191; https://doi.org/10.3390/molecules22020191 - 24 Jan 2017

Cited by 392 | Viewed by 63921

Abstract

Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, [...] Read more.

Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma. Full article

(This article belongs to the Special Issue Silymarin)

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26 pages, 5645 KiB

Open AccessReview

The Therapeutic Potential of Migrastatin-Core Analogs for the Treatment of Metastatic Cancer

by Ernest Giralt^1,2 and Daniele Lo Re^1,*

¹ Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, C/Baldiri Reixac 10, Barcelona E-08028, Spain

² Department of Organic Chemistry, University of Barcelona, Marti i Franques 1-11, Barcelona E-08028, Spain

Molecules 2017, 22(2), 198; https://doi.org/10.3390/molecules22020198 - 9 Feb 2017

Cited by 5 | Viewed by 7939

Abstract

Tumor metastasis is a complex process in which cells detach from the primary tumor and colonize a distant organ. Metastasis is also the main process responsible for cancer-related death. Despite the enormous efforts made to unravel the metastatic process, there is no effective [...] Read more.

Tumor metastasis is a complex process in which cells detach from the primary tumor and colonize a distant organ. Metastasis is also the main process responsible for cancer-related death. Despite the enormous efforts made to unravel the metastatic process, there is no effective therapy, and patients with metastatic tumors have poor prognosis. In this regard, there is an urgent need for new therapeutic tools for the treatment of this disease. Small molecules with the capacity to reduce cell migration could be used to treat metastasis. Migrastatin-core analogs are naturally inspired macrocycles that inhibit pathological cell migration and are able to reduce metastasis in animal models. Migrastatin analogs can be synthesized from a common advanced intermediate. Herein we present a review of the synthetic approaches that can be used to prepare this key intermediate, together with a review of the biological activity of migrastatin-core analogs and current hypotheses concerning their mechanism of action. Full article

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

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28 pages, 3625 KiB

Open AccessReview

Recent Advances in Macrocyclic Fluorescent Probes for Ion Sensing

by Joseph K.-H. Wong, Matthew H. Todd and Peter J. Rutledge^*

School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia

Molecules 2017, 22(2), 200; https://doi.org/10.3390/molecules22020200 - 25 Jan 2017

Cited by 63 | Viewed by 9620

Abstract

Small-molecule fluorescent probes play a myriad of important roles in chemical sensing. Many such systems incorporating a receptor component designed to recognise and bind a specific analyte, and a reporter or transducer component which signals the binding event with a change in fluorescence [...] Read more.

Small-molecule fluorescent probes play a myriad of important roles in chemical sensing. Many such systems incorporating a receptor component designed to recognise and bind a specific analyte, and a reporter or transducer component which signals the binding event with a change in fluorescence output have been developed. Fluorescent probes use a variety of mechanisms to transmit the binding event to the reporter unit, including photoinduced electron transfer (PET), charge transfer (CT), Förster resonance energy transfer (FRET), excimer formation, and aggregation induced emission (AIE) or aggregation caused quenching (ACQ). These systems respond to a wide array of potential analytes including protons, metal cations, anions, carbohydrates, and other biomolecules. This review surveys important new fluorescence-based probes for these and other analytes that have been reported over the past five years, focusing on the most widely exploited macrocyclic recognition components, those based on cyclam, calixarenes, cyclodextrins and crown ethers; other macrocyclic and non-macrocyclic receptors are also discussed. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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10 pages, 1500 KiB

Open AccessReview

Metal Fluorides, Metal Chlorides and Halogenated Metal Oxides as Lewis Acidic Heterogeneous Catalysts. Providing Some Context for Nanostructured Metal Fluorides

by David Lennon and John M. Winfield^*

School of Chemistry, University of Glasgow, G12 8QQ Glasgow, UK

Molecules 2017, 22(2), 201; https://doi.org/10.3390/molecules22020201 - 28 Jan 2017

Cited by 7 | Viewed by 7699

Abstract

Aspects of the chemistry of selected metal fluorides, which are pertinent to their real or potential use as Lewis acidic, heterogeneous catalysts, are reviewed. Particular attention is paid to β-aluminum trifluoride, aluminum chlorofluoride and aluminas γ and η, whose surfaces become partially fluorinated [...] Read more.

Aspects of the chemistry of selected metal fluorides, which are pertinent to their real or potential use as Lewis acidic, heterogeneous catalysts, are reviewed. Particular attention is paid to β-aluminum trifluoride, aluminum chlorofluoride and aluminas γ and η, whose surfaces become partially fluorinated or chlorinated, through pre-treatment with halogenating reagents or during a catalytic reaction. In these cases, direct comparisons with nanostructured metal fluorides are possible. In the second part of the review, attention is directed to iron(III) and copper(II) metal chlorides, whose Lewis acidity and potential redox function have had important catalytic implications in large-scale chlorohydrocarbons chemistry. Recent work, which highlights the complexity of reactions that can occur in the presence of supported copper(II) chloride as an oxychlorination catalyst, is featured. Although direct comparisons with nanostructured fluorides are not currently possible, the work could be relevant to possible future catalytic developments in nanostructured materials. Full article

(This article belongs to the Special Issue Nano-sized Metal Fluorides: Novel Approaches to Lewis Acid Catalysts)

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16 pages, 247 KiB

Open AccessReview

Hyperuricaemia, Xanthine Oxidoreductase and Ribosome‐Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research

by Andrea Bolognesi^†

, Massimo Bortolotti^†

, Maria Giulia Battelli^*

and Letizia Polito

¹ Department of Experimental, Diagnostic and Specialty Medicine‐DIMES, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy

^† These authors contributed equally to this paper.

Molecules 2017, 22(2), 206; https://doi.org/10.3390/molecules22020206 - 27 Jan 2017

Cited by 4 | Viewed by 5440

Abstract

The enzymes called ribosome‐inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these [...] Read more.

The enzymes called ribosome‐inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these studies has been one of the most relevant. After a short biographical introduction, an overview is offered of the main results obtained by his investigations during last 55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs. Full article

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

34 pages, 2257 KiB

Open AccessReview

Cytotoxic Compounds Derived from Marine Sponges. A Review (2010–2012)

by Roberto Mioso^1,*, Francisco J. Toledo Marante², Ranilson De Souza Bezerra¹, Flávio Valadares Pereira Borges³, Bárbara V. de Oliveira Santos^4,* and Irma Herrera Bravo de Laguna^5,*

¹ Laboratory of Enzymology – LABENZ, Department of Biochemistry, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil

² Department of Chemistry, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria 35017, Spain

³ Post-Graduation Program in Natural Products and Synthetic Bioactives, Federal University of Paraíba, João Pessoa 58051-970, Paraíba, Brazil

⁴ Post-Graduation Program in Development and Technological Innovation in Medicines, Department of Pharmaceutical Sciences, Federal University of Paraiba, João Pessoa 58051-900, Paraíba, Brazil

⁵ Department of Biology, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria 35017, Spain

Molecules 2017, 22(2), 208; https://doi.org/10.3390/molecules22020208 - 28 Jan 2017

Cited by 50 | Viewed by 8971

Abstract

Abstract: This extensive review covers research published between 2010 and 2012 regarding new compounds derived from marine sponges, including 62 species from 60 genera belonging to 33 families and 13 orders of the Demospongia class (Porifera). The emphasis is on the cytotoxic [...] Read more.

Abstract: This extensive review covers research published between 2010 and 2012 regarding new compounds derived from marine sponges, including 62 species from 60 genera belonging to 33 families and 13 orders of the Demospongia class (Porifera). The emphasis is on the cytotoxic activity that bioactive metabolites from sponges may have on cancer cell lines. At least 197 novel chemical structures from 337 compounds isolated have been found to support this work. Details on the source and taxonomy of the sponges, their geographical occurrence, and a range of chemical structures are presented. The compounds discovered from the reviewed marine sponges fall into mainly four chemical classes: terpenoids (41.9%), alkaloids (26.2%), macrolides (8.9%) and peptides (6.3%) which, along with polyketides, sterols, and others show a range of biological activities. The key sponge orders studied in the reviewed research were Dictyoceratida, Haplosclerida, Tetractinellida, Poecilosclerida, and Agelasida. Petrosia, Haliclona (Haplosclerida), Rhabdastrella (Tetractinellida), Coscinoderma and Hyppospongia (Dictyioceratida), were found to be the most promising genera because of their capacity for producing new bioactive compounds. Several of the new compounds and their synthetic analogues have shown in vitro cytotoxic and pro-apoptotic activities against various tumor/cancer cell lines, and some of them will undergo further in vivo evaluation. Full article

(This article belongs to the Section Natural Products Chemistry)

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12 pages, 1547 KiB

Open AccessReview

Actions of Quercetin, a Polyphenol, on Blood Pressure

by Yoshinori Marunaka^1,2,3,*

, Rie Marunaka^1,4, Hongxin Sun¹, Toshiro Yamamoto⁴, Narisato Kanamura⁴, Toshio Inui^1,2,5 and Akiyuki Taruno¹

¹ Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

² Department of Bio-Ionomics, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

³ Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto 602-8013, Japan

⁴ Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

⁵ Saisei Mirai Clinics, Moriguchi 570-0012, Japan

Molecules 2017, 22(2), 209; https://doi.org/10.3390/molecules22020209 - 29 Jan 2017

Cited by 150 | Viewed by 17056

Abstract

Disorder of blood pressure control causes serious diseases in the cardiovascular system. This review focuses on the anti-hypertensive action of quercetin, a flavonoid, which is one of the polyphenols characterized as the compounds containing large multiples of phenol structural units, by varying the [...] Read more.

Disorder of blood pressure control causes serious diseases in the cardiovascular system. This review focuses on the anti-hypertensive action of quercetin, a flavonoid, which is one of the polyphenols characterized as the compounds containing large multiples of phenol structural units, by varying the values of various blood pressure regulatory factors, such as vascular compliance, peripheral vascular resistance, and total blood volume via anti-inflammatory and anti-oxidant actions. In addition to the anti-inflammatory and anti-oxidant actions of quercetin, we especially describe a novel mechanism of quercetin’s action on the cytosolic Cl⁻ concentration ([Cl⁻]_c) and novel roles of the cytosolic Cl⁻ i.e.: (1) quercetin elevates [Cl⁻]_c by activating Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1) in renal epithelial cells contributing to Na⁺ reabsorption via the epithelial Na⁺ channel (ENaC); (2) the quercetin-induced elevation of [Cl⁻]_c in renal epithelial cells diminishes expression of ENaC leading to a decrease in renal Na⁺ reabsorption; and (3) this reduction of ENaC-mediated Na⁺ reabsorption in renal epithelial cells drops volume-dependent elevated blood pressure. In this review, we introduce novel, unique mechanisms of quercetin’s anti-hypertensive action via activation of NKCC1 in detail. Full article

(This article belongs to the Special Issue Polyphenols and Cardiovascular Disease)

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12 pages, 2434 KiB

Open AccessReview

Evolution of Complex Target SELEX to Identify Aptamers against Mammalian Cell-Surface Antigens

by Prabodhika Mallikaratchy^1,2,3

¹ Department of Chemistry, Lehman College, The City University of New York, 250 Bedford Park Blvd. West, Bronx, NY 10468, USA

² Ph.D. Programs in Chemistry and Biochemistry, CUNY Graduate Center 365 Fifth Avenue, New York, NY 10016, USA

³ Ph.D. Program in Molecular, Cellular and Developmental Biology, CUNY Graduate Center 365 Fifth Avenue, New York, NY 10016, USA

Molecules 2017, 22(2), 215; https://doi.org/10.3390/molecules22020215 - 30 Jan 2017

Cited by 77 | Viewed by 10721

Abstract

The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a [...] Read more.

The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This review summarizes these milestones that have pushed the field forward, allowing researchers to generate aptamers that can potentially be applied as therapeutic and diagnostic agents. Full article

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

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22 pages, 7488 KiB

Open AccessReview

In Situ Coupling of Ultrasound to Electro- and Photo-Deposition Methods for Materials Synthesis

by Agnieszka Magdziarz^* and Juan C. Colmenares^*

Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland

Molecules 2017, 22(2), 216; https://doi.org/10.3390/molecules22020216 - 31 Jan 2017

Cited by 26 | Viewed by 6526

Abstract

This short review provides the current state-of-the-art of in situ coupling of ultrasound to chemical deposition methods. A synergetic action of the ultrasound and light radiation or electrical fields may result in new powerful methodologies, and these include sonophotodeposition and sonoelectrodeposition processes. The [...] Read more.

This short review provides the current state-of-the-art of in situ coupling of ultrasound to chemical deposition methods. A synergetic action of the ultrasound and light radiation or electrical fields may result in new powerful methodologies, and these include sonophotodeposition and sonoelectrodeposition processes. The effect of ultrasound is explained on the base of different physical mechanisms emerging from cavitation phenomenon. Some possible mechanisms of the interactions between ultrasound and photochemical and electrochemical processes are discussed here. The application of sonophotodeposition and sonoelectrodeposition as green energy sources in the syntheses of different nanomaterials is also reviewed. Full article

(This article belongs to the Special Issue Sonochemistry and Green Chemistry Applications)

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14 pages, 573 KiB

Open AccessReview

Regulation of T Cell Activation and Differentiation by Extracellular Vesicles and Their Pathogenic Role in Systemic Lupus Erythematosus and Multiple Sclerosis

by Cristina Ulivieri^*

and Cosima T. Baldari

Department of Life Sciences, University of Siena, Via Aldo Moro, 2 53100, Siena, Italy

Molecules 2017, 22(2), 225; https://doi.org/10.3390/molecules22020225 - 2 Feb 2017

Cited by 24 | Viewed by 9798

Abstract

How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and [...] Read more.

How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and infiltrate into the target tissues where their reactivation by peripheral tissue antigen is a prerequisite for effector cytokine production and tissue destruction. The target tissue microenvironment, as well as the local microenvironment at the immune synapse formed by T cells that encounter cognate antigen presenting cells (APCs) shave recently emerged as critical factors in shaping the differentiation and function of self-reactive effector T cells, providing the signals required for their activation in the form of the self-antigen and cytokine milieu. Moreover, depending on the specific microenvironment, self-reactive effector T cells have the ability to change their phenotype, especially Th17 and regulatory T (Treg) cells, which are characterized by the highest instability. In this context, cell-derived extracellular vesicles, i.e., vesicles carrying cytosolic proteins and nucleic acids protected by a phospholipid bilayer, as well as membrane-associated proteins, with the ability to spread throughout the body by means of biological fluids, are emerging as key mediators in intercellular communications and in the modulation of the microenvironment. In this review, we will discuss recent findings implicating extracellular vesicles (EVs) at different steps of CD4+ T cell differentiation to specific effectors, with a focus on the Th17/Treg balance and its alterations in systemic lupus erythematosus and multiple sclerosis. Full article

(This article belongs to the Special Issue Molecules Mediating Allergic and Autoimmune Inflammation: Commemorative Issue in Honor of Professor Christopher W. K. Lam’s Research Achievements on the Occasion of His 70th Birthday)

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21 pages, 2768 KiB

Open AccessReview

Electrospun Fibers of Cyclodextrins and Poly(cyclodextrins)

by Alejandro Costoya, Angel Concheiro

and Carmen Alvarez-Lorenzo^*

Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, R+D Pharma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15872 Santiago de Compostela, Spain

Molecules 2017, 22(2), 230; https://doi.org/10.3390/molecules22020230 - 3 Feb 2017

Cited by 50 | Viewed by 9158

Abstract

Cyclodextrins (CDs) can endow electrospun fibers with outstanding performance characteristics that rely on their ability to form inclusion complexes. The inclusion complexes can be blended with electrospinnable polymers or used themselves as main components of electrospun nanofibers. In general, the presence of CDs [...] Read more.

Cyclodextrins (CDs) can endow electrospun fibers with outstanding performance characteristics that rely on their ability to form inclusion complexes. The inclusion complexes can be blended with electrospinnable polymers or used themselves as main components of electrospun nanofibers. In general, the presence of CDs promotes drug release in aqueous media, but they may also play other roles such as protection of the drug against adverse agents during and after electrospinning, and retention of volatile fragrances or therapeutic agents to be slowly released to the environment. Moreover, fibers prepared with empty CDs appear particularly suitable for affinity separation. The interest for CD-containing nanofibers is exponentially increasing as the scope of applications is widening. The aim of this review is to provide an overview of the state-of-the-art on CD-containing electrospun mats. The information has been classified into three main sections: (i) fibers of mixtures of CDs and polymers, including polypseudorotaxanes and post-functionalization; (ii) fibers of polymer-free CDs; and (iii) fibers of CD-based polymers (namely, polycyclodextrins). Processing conditions and applications are analyzed, including possibilities of development of stimuli-responsive fibers. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry)

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17 pages, 1375 KiB

Open AccessReview

Chromatographic Separation of Vitamin E Enantiomers

by Ju-Yen Fu¹, Thet-Thet Htar², Leanne De Silva², Doryn Meam-Yee Tan¹ and Lay-Hong Chuah^2,*

¹ Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia

² School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia

Molecules 2017, 22(2), 233; https://doi.org/10.3390/molecules22020233 - 4 Feb 2017

Cited by 19 | Viewed by 8245

Abstract

Vitamin E is recognized as an essential vitamin since its discovery in 1922. Most vegetable oils contain a mixture of tocopherols and tocotrienols in the vitamin E composition. Structurally, tocopherols and tocotrienols share a similar chromanol ring and a side chain at the [...] Read more.

Vitamin E is recognized as an essential vitamin since its discovery in 1922. Most vegetable oils contain a mixture of tocopherols and tocotrienols in the vitamin E composition. Structurally, tocopherols and tocotrienols share a similar chromanol ring and a side chain at the C-2 position. Owing to the three chiral centers in tocopherols, they can appear as eight different stereoisomers. Plant sources of tocopherol are naturally occurring in the form of RRR while synthetic tocopherols are usually in the form of all-racemic mixture. Similarly, with only one chiral center, natural tocotrienols occur as the R-isoform. In this review, we aim to discuss a few chromatographic methods that had been used to separate the stereoisomers of tocopherols and tocotrienols. These methods include high performance liquid chromatography, gas chromatography and combination of both. The review will focus on method development including selection of chiral columns, detection method and choice of elution solvent in the context of separation efficiency, resolution and chiral purity. The applications for separation of enantiomers in vitamin E will also be discussed especially in terms of the distinctive biological potency among the stereoisoforms. Full article

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

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18 pages, 6055 KiB

Open AccessReview

Towards Precision Engineering of Canonical Polyketide Synthase Domains: Recent Advances and Future Prospects

by Carmen L. Bayly^1,2 and Vikramaditya G. Yadav^2,*

¹ Department of Genome Sciences & Technology, The University of British Columbia, Vancouver, BC V5Z 4S6, Canada

² Department of Chemical & Biological Engineering, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada

Molecules 2017, 22(2), 235; https://doi.org/10.3390/molecules22020235 - 5 Feb 2017

Cited by 22 | Viewed by 10926

Abstract

Modular polyketide synthases (mPKSs) build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules) of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause [...] Read more.

Modular polyketide synthases (mPKSs) build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules) of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause both unintended products and dramatically reduced activity. This limits the engineering and combinatorial potential of mPKSs, precluding access to further potential therapeutics. Different regions on a given mPKS domain determine how it interacts both with its substrate and with other domains. Within the assembly line, these interactions are crucial to the proper ordering of reactions and efficient polyketide construction. Achieving control over these domain functions, through precision engineering at key regions, would greatly expand our catalogue of accessible polyketide products. Canonical mPKS domains, given that they are among the most well-characterized, are excellent candidates for such fine-tuning. The current minireview summarizes recent advances in the mechanistic understanding and subsequent precision engineering of canonical mPKS domains, focusing largely on developments in the past year. Full article

(This article belongs to the Special Issue Polyketides)

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21 pages, 5536 KiB

Open AccessReview

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

by Márcio S. Silva

Centro de Ciências Naturais e Humanas—CCNH—Universidade Federal do ABC—UFABC, Av. Dos Estados 5001, 09210-180 Santo André –SP, Brazil

Molecules 2017, 22(2), 247; https://doi.org/10.3390/molecules22020247 - 7 Feb 2017

Cited by 74 | Viewed by 15440

Abstract

Nuclear magnetic resonance (NMR) is a powerful tool for the elucidation of chemical structure and chiral recognition. In the last decade, the number of probes, media, and experiments to analyze chiral environments has rapidly increased. The evaluation of chiral molecules and systems has [...] Read more.

Nuclear magnetic resonance (NMR) is a powerful tool for the elucidation of chemical structure and chiral recognition. In the last decade, the number of probes, media, and experiments to analyze chiral environments has rapidly increased. The evaluation of chiral molecules and systems has become a routine task in almost all NMR laboratories, allowing for the determination of molecular connectivities and the construction of spatial relationships. Among the features that improve the chiral recognition abilities by NMR is the application of different nuclei. The simplicity of the multinuclear NMR spectra relative to ¹H, the minimal influence of the experimental conditions, and the larger shift dispersion make these nuclei especially suitable for NMR analysis. Herein, the recent advances in multinuclear (¹⁹F, ³¹P, ¹³C, and ⁷⁷Se) NMR spectroscopy for chiral recognition of organic compounds are presented. The review describes new chiral derivatizing agents and chiral solvating agents used for stereodiscrimination and the assignment of the absolute configuration of small organic compounds. Full article

(This article belongs to the Section Organic Chemistry)

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22 pages, 1465 KiB

Open AccessReview

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

by Zeina Habli¹, Georgio Toumieh¹, Maamoun Fatfat¹, Omar Nasser Rahal² and Hala Gali-Muhtasib^1,*

¹ Department of Biology and Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut 1107 2020, Lebanon

² School of Medicine, Saba University School of Medicine, Saba, Dutch Caribbean 5016121, The Netherlands

Molecules 2017, 22(2), 250; https://doi.org/10.3390/molecules22020250 - 8 Feb 2017

Cited by 127 | Viewed by 11207

Abstract

Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an [...] Read more.

Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery. Full article

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

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16 pages, 1869 KiB

Open AccessReview

A Guide to the Variability of Flavonoids in Brassica oleracea

by Vera Mageney¹, Susanne Neugart² and Dirk C. Albach^1,*

¹ Institute of Biology and Environmental Sciences, Carl von Ossietzky University, Oldenburg Carl von Ossietzky Str. 9-11, 26129 Oldenburg, Germany

² Leibniz-Institute of Vegetables and Ornamental Crops Grossbeeren/Erfurt e. V., Theodor-Echtermeyer-Weg 1, 14979 Grossbeeren, Germany

Molecules 2017, 22(2), 252; https://doi.org/10.3390/molecules22020252 - 8 Feb 2017

Cited by 43 | Viewed by 7789

Abstract

Flavonoids represent a typical secondary metabolite class present in cruciferous vegetables. Their potential as natural antioxidants has raised considerable scientific interest. Impacts on the human body after food consumption as well as their effect as pharmaceutical supplements are therefore under investigation. Their numerous [...] Read more.

Flavonoids represent a typical secondary metabolite class present in cruciferous vegetables. Their potential as natural antioxidants has raised considerable scientific interest. Impacts on the human body after food consumption as well as their effect as pharmaceutical supplements are therefore under investigation. Their numerous physiological functions make them a promising tool for breeding purposes. General methods for flavonoid analysis are well established, though new compounds are still being identified. However, differences in environmental circumstances of the studies and analytical methods impede comparability of quantification results. To promote future investigations on flavonoids in cruciferous plants we provide a checklist on best-practice in flavonoid research and specific flavonoid derivatives that are valuable targets for further research, choosing a representative species of scientific interest, Brassica oleracea. Full article

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13 pages, 3084 KiB

Open AccessReview

β-Glucans: Relationships between Modification, Conformation and Functional Activities

by Qiang Wang¹, Xiaojing Sheng¹, Aimin Shi¹, Hui Hu¹, Ying Yang¹, Li Liu¹, Ling Fei² and Hongzhi Liu^1,*

¹ Institute of Food Science and Technology, Chinese Academy of Agriculture Sciences, Beijing 100193, China

² Cornell University, Robert Frederick Smith School of Chemical and Biomolecular Engineering, Ithaca, NY 14850, USA

Molecules 2017, 22(2), 257; https://doi.org/10.3390/molecules22020257 - 9 Feb 2017

Cited by 144 | Viewed by 12346

Abstract

β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role [...] Read more.

β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role on its biological activities. Therefore, β-glucans obtained from different sources, while sharing the same basic structures, often show different bioactivities. The basic structure and inter-molecular forces of polysaccharides can be changed by modification, which leads to the conformational transformation in solution that can directly affect bioactivity. In this review, we will first determine different ways to modify β-glucan molecules including physical methods, chemical methods, and biological methods, and then reveal the relationship of the flexible helix form of the molecule chain and the helix conformation to their bioactivities. Last, we summarize the scientific challenges to modifying β-glucan’s conformation and functional activity, and discuss its potential future development. Full article

(This article belongs to the Special Issue Natural Polysaccharides)

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37 pages, 4416 KiB

Open AccessReview

The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites

by Alberto Guevara-Flores, José De Jesús Martínez-González, Juan Luis Rendón and Irene Patricia Del Arenal^*

Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70-159, 04510 Mexico City, Mexico

Molecules 2017, 22(2), 259; https://doi.org/10.3390/molecules22020259 - 10 Feb 2017

Cited by 29 | Viewed by 9297

Abstract

The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To [...] Read more.

The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To contend with such harmful compounds, living organisms have evolved antioxidant strategies. In this sense, the thiol-dependent antioxidant defense systems play a central role. In all cases, cysteine constitutes the major building block on which such systems are constructed, being present in redox substrates such as glutathione, thioredoxin, and trypanothione, as well as at the catalytic site of a variety of reductases and peroxidases. In some cases, the related selenocysteine was incorporated at selected proteins. In invertebrate parasites, antioxidant systems have evolved in a diversity of both substrates and enzymes, representing a potential area in the design of anti-parasite strategies. The present review focus on the organization of the thiol-based antioxidant systems in invertebrate parasites. Differences between these taxa and its final mammal host is stressed. An understanding of the antioxidant defense mechanisms in this kind of parasites, as well as their interactions with the specific host is crucial in the design of drugs targeting these organisms. Full article

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

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34 pages, 11873 KiB

Open AccessReview

Porous Hydrogen-Bonded Organic Frameworks

by Yi-Fei Han^1,2, Ying-Xue Yuan^1,2 and Hong-Bo Wang^1,2,*

¹ Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, School of Chemical and Environmental Engineering, Jianghan University, Wuhan 430056, Hubei, China

² College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, China

Molecules 2017, 22(2), 266; https://doi.org/10.3390/molecules22020266 - 13 Feb 2017

Cited by 108 | Viewed by 15612

Abstract

Ordered porous solid-state architectures constructed via non-covalent supramolecular self-assembly have attracted increasing interest due to their unique advantages and potential applications. Porous metal-coordination organic frameworks (MOFs) are generated by the assembly of metal coordination centers and organic linkers. Compared to MOFs, porous hydrogen-bonded [...] Read more.

Ordered porous solid-state architectures constructed via non-covalent supramolecular self-assembly have attracted increasing interest due to their unique advantages and potential applications. Porous metal-coordination organic frameworks (MOFs) are generated by the assembly of metal coordination centers and organic linkers. Compared to MOFs, porous hydrogen-bonded organic frameworks (HOFs) are readily purified and recovered via simple recrystallization. However, due to lacking of sufficiently ability to orientate self-aggregation of building motifs in predictable manners, rational design and preparation of porous HOFs are still challenging. Herein, we summarize recent developments about porous HOFs and attempt to gain deeper insights into the design strategies of basic building motifs. 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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14 pages, 923 KiB

Open AccessReview

Anticancer Activities of C₁₈-, C₁₉-, C₂₀-, and Bis-Diterpenoid Alkaloids Derived from Genus Aconitum

by Meng-Yue Ren^1,2, Qing-Tian Yu^1,2, Chun-Yu Shi^1,2 and Jia-Bo Luo^1,2,*

¹ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

² Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou 510515, China

Molecules 2017, 22(2), 267; https://doi.org/10.3390/molecules22020267 - 13 Feb 2017

Cited by 38 | Viewed by 6834

Abstract

Cancer is one of the most common lethal diseases, and natural products have been extensively studied as anticancer agents considering their availability, low toxicity, and economic affordability. Plants belonging to the genus Aconitum have been widely used medically in many Asian countries since [...] Read more.

Cancer is one of the most common lethal diseases, and natural products have been extensively studied as anticancer agents considering their availability, low toxicity, and economic affordability. Plants belonging to the genus Aconitum have been widely used medically in many Asian countries since ancient times. These plants have been proven effective for treating several types of cancer, such as lung, stomach, and liver cancers. The main effective components of Aconitum plants are diterpenoid alkaloids—which are divided into C₁₈-, C₁₉-, C₂₀-, and bis-diterpenoid alkaloids—are reportedly some of the most promising, naturally abundant compounds for treating cancer. This review focuses on the progress of diterpenoid alkaloids with different structures derived from Aconitum plants and some of their derivatives with potential anticancer activities. We hope that this work can serve as a reference for further developing Aconitum diterpenoid alkaloids as anticancer agents. Full article

(This article belongs to the Special Issue Diterpene and Its Significance in Natural Medicine)

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24 pages, 632 KiB

Open AccessReview

Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review

by Oludemi Taofiq^1,2,3

, Ana M. González-Paramás²

, Maria Filomena Barreiro³ and Isabel C. F. R. Ferreira^1,*

¹ Mountain Research Centre (CIMO), ESA, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1172, 5300-253 Bragança, Portugal

² Grupo de Investigación en Polifenoles (GIP), Unidad de Nutrición y Bromatología, Faculty of Pharmacy, University of Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain

³ Laboratory of Separation and Reaction Engineering (LSRE), Associate Laboratory LSRE/LCM, Polytechnic Institute of Bragança, Campus de Santa Apolónia, 1134, 5301-857 Bragança, Portugal

Molecules 2017, 22(2), 281; https://doi.org/10.3390/molecules22020281 - 13 Feb 2017

Cited by 320 | Viewed by 18828

Abstract

Bioactive compounds from natural sources, due to their widely-recognized benefits, have been exploited as cosmeceutical ingredients. Among them, phenolic acids emerge with a very interesting potential. In this context, this review analyzes hydroxycinnamic acids and their derivatives as multifunctional ingredients for topical application, [...] Read more.

Bioactive compounds from natural sources, due to their widely-recognized benefits, have been exploited as cosmeceutical ingredients. Among them, phenolic acids emerge with a very interesting potential. In this context, this review analyzes hydroxycinnamic acids and their derivatives as multifunctional ingredients for topical application, as well as the limitations associated with their use in cosmetic formulations. Hydroxycinnamic acids and their derivatives display antioxidant, anti-collagenase, anti-inflammatory, antimicrobial and anti-tyrosinase activities, as well as ultraviolet (UV) protective effects, suggesting that they can be exploited as anti-aging and anti-inflammatory agents, preservatives and hyperpigmentation-correcting ingredients. Due to their poor stability, easy degradation and oxidation, microencapsulation techniques have been employed for topical application, preventing them from degradation and enabling a sustained release. Based on the above findings, hydroxycinnamic acids present high cosmetic potential, but studies addressing the validation of their benefits in cosmetic formulations are still scarce. Furthermore, studies dealing with skin permeation are scarcely available and need to be conducted in order to predict the topical bioavailability of these compounds after application. Full article

(This article belongs to the Collection Bioactive Compounds)

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48 pages, 1749 KiB

Open AccessReview

Addressing Facts and Gaps in the Phenolics Chemistry of Winery By-Products

by Nelson F. L. Machado¹ and Raúl Domínguez-Perles^1,2,*

¹ Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes e Alto Douro (CITAB-UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal

² Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), Campus University, Edif. 25, Espinardo, 30100 Murcia, Spain

Molecules 2017, 22(2), 286; https://doi.org/10.3390/molecules22020286 - 14 Feb 2017

Cited by 54 | Viewed by 8075

Abstract

Grape and wine phenolics display a noticeable structural diversity, encompassing distinct compounds ranging from simple molecules to oligomers, as well as polymers usually designated as tannins. Since these compounds contribute critically to the organoleptic properties of wines, their analysis and quantification are of [...] Read more.

Grape and wine phenolics display a noticeable structural diversity, encompassing distinct compounds ranging from simple molecules to oligomers, as well as polymers usually designated as tannins. Since these compounds contribute critically to the organoleptic properties of wines, their analysis and quantification are of primordial importance for winery industry operators. Besides, the occurrence of these compounds has been also extensively described in winery residues, which have been pointed as a valuable source of bioactive phytochemicals presenting potential for the development of new added value products that could fit the current market demands. Therefore, the cumulative knowledge generated during the last decades has allowed the identification of the most promising compounds displaying interesting biological functions, as well as the chemical features responsible for the observed bioactivities. In this regard, the present review explores the scope of the existing knowledge, concerning the compounds found in these winery by-products, as well as the chemical features presumably responsible for the biological functions already identified. Moreover, the present work will hopefully pave the way for further actions to develop new powerful applications to these materials, thus, contributing to more sustainable valorization procedures and the development of newly obtained compounds with enhanced biological properties. Full article

(This article belongs to the Collection Wine Chemistry)

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50 pages, 2798 KiB

Open AccessReview

Calamintha nepeta (L.) Savi and its Main Essential Oil Constituent Pulegone: Biological Activities and Chemistry

by Mijat Božović¹

and Rino Ragno^1,2,*

¹ Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy

² Alchemical Dynamics s.r.l., 00125 Rome, Italy

Molecules 2017, 22(2), 290; https://doi.org/10.3390/molecules22020290 - 14 Feb 2017

Cited by 85 | Viewed by 15341

Abstract

Medicinal plants play an important role in the treatment of a wide range of diseases, even if their chemical constituents are not always completely recognized. Observations on their use and efficacy significantly contribute to the disclosure of their therapeutic properties. Calamintha nepeta (L.) [...] Read more.

Medicinal plants play an important role in the treatment of a wide range of diseases, even if their chemical constituents are not always completely recognized. Observations on their use and efficacy significantly contribute to the disclosure of their therapeutic properties. Calamintha nepeta (L.) Savi is an aromatic herb with a mint-oregano flavor, used in the Mediterranean areas as a traditional medicine. It has an extensive range of biological activities, including antimicrobial, antioxidant and anti-inflammatory, as well as anti-ulcer and insecticidal properties. This study aims to review the scientific findings and research reported to date on Calamintha nepeta (L.) Savi that prove many of the remarkable various biological actions, effects and some uses of this species as a source of bioactive natural compounds. On the other hand, pulegone, the major chemical constituent of Calamintha nepeta (L.) Savi essential oil, has been reported to exhibit numerous bioactivities in cells and animals. Thus, this integrated overview also surveys and interprets the present knowledge of chemistry and analysis of this oxygenated monoterpene, as well as its beneﬁcial bioactivities. Areas for future research are suggested Full article

(This article belongs to the Special Issue Essential Oils: Chemistry and Bioactivity)

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30 pages, 1021 KiB

Open AccessReview

Wine Flavonoids in Health and Disease Prevention

by Iva Fernandes

, Rosa Pérez-Gregorio, Susana Soares, Nuno Mateus^*

and Victor De Freitas

LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal

Molecules 2017, 22(2), 292; https://doi.org/10.3390/molecules22020292 - 14 Feb 2017

Cited by 199 | Viewed by 20826

Abstract

Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, [...] Read more.

Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue. Nevertheless, there are several reports on the health protective properties of wine phenolics for several diseases such as cardiovascular diseases, some cancers, obesity, neurodegenerative diseases, diabetes, allergies and osteoporosis. The different interactions that wine flavonoids may have with key biological targets are crucial for some of these health-promoting effects. The interaction between some wine flavonoids and some specific enzymes are one example. The way wine flavonoids may be absorbed and metabolized could interfere with their bioavailability and therefore in their health-promoting effect. Hence, some reports have focused on flavonoids absorption, metabolism, microbiota effect and overall on flavonoids bioavailability. This review summarizes some of these major issues which are directly related to the potential health-promoting effects of wine flavonoids. Reports related to flavonoids and health highlight some relevant scientific information. However, there is still a gap between the knowledge of wine flavonoids bioavailability and their health-promoting effects. More in vivo results as well as studies focused on flavonoid metabolites are still required. Moreover, it is also necessary to better understand how biological interactions (with microbiota and cells, enzymes or general biological systems) could interfere with flavonoid bioavailability. Full article

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

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18 pages, 2001 KiB

Open AccessReview

An Overview of Stress-Induced Resveratrol Synthesis in Grapes: Perspectives for Resveratrol-Enriched Grape Products

by Mohidul Hasan and Hanhong Bae^*

Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Korea

Molecules 2017, 22(2), 294; https://doi.org/10.3390/molecules22020294 - 14 Feb 2017

Cited by 184 | Viewed by 14820

Abstract

Resveratrol is the most important stilbene phytoalexin synthesized naturally or induced in plants, as a part of their defense mechanism. Grapes and their derivative products, including juice and wine, are the most important natural sources of resveratrol, consisting of notably higher amounts than [...] Read more.

Resveratrol is the most important stilbene phytoalexin synthesized naturally or induced in plants, as a part of their defense mechanism. Grapes and their derivative products, including juice and wine, are the most important natural sources of resveratrol, consisting of notably higher amounts than other natural sources like peanuts. Consumption of red wine with its presence of resveratrol explained the “French Paradox”. Hence, the demand of resveratrol from grapes is increasing. Moreover, as a natural source of resveratrol, grapes became very important in the nutraceutical industry for their benefits to human health. The accumulation of resveratrol in grape skin, juice, and wine has been found to be induced by the external stimuli: microbial infection, ultrasonication (US) treatment, light-emitting diode (LED), ultra violet (UV) irradiation, elicitors or signaling compounds, macronutrients, and fungicides. Phenylalanine ammonia lyase, cinnamate-4-hydroxylase, coumaroyl-CoA ligase, and stilbene synthase play a key role in the synthesis of resveratrol. The up-regulation of those genes have the positive relationship with the elicited accumulation of resveratrol. In this review, we encapsulate the effect of different external stimuli (biotic and abiotic stresses or signaling compounds) in order to obtain the maximum accumulation of resveratrol in grape skin, leaves, juice, wine, and cell cultures. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3962 KiB

Open AccessReview

Adamantane in Drug Delivery Systems and Surface Recognition

by Adela Štimac¹, Marina Šekutor², Kata Mlinarić-Majerski², Leo Frkanec²

and Ruža Frkanec^1,*

¹ University of Zagreb, Centre for Research and Knowledge Transfer in Biotechnology, Rockefellerova 10, 10000 Zagreb, Croatia

² Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia

Molecules 2017, 22(2), 297; https://doi.org/10.3390/molecules22020297 - 16 Feb 2017

Cited by 143 | Viewed by 15234

Abstract

The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in [...] Read more.

The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application. Full article

(This article belongs to the Special Issue Diamondoids and Their Derivatives)

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23 pages, 649 KiB

Open AccessReview

A Review on the Phytochemistry, Pharmacology, and Pharmacokinetics of Amentoflavone, a Naturally-Occurring Biflavonoid

by Sheng Yu¹, Hui Yan¹, Li Zhang¹, Mingqiu Shan^1,2,*

, Peidong Chen¹, Anwei Ding¹ and Sam Fong Yau Li²

¹ Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China

² Department of Chemistry, National University of Singapore, Singapore 117543, Singapore

Molecules 2017, 22(2), 299; https://doi.org/10.3390/molecules22020299 - 16 Feb 2017

Cited by 161 | Viewed by 14745

Abstract

Amentoflavone (C₃₀H₁₈O₁₀) is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and [...] Read more.

Amentoflavone (C₃₀H₁₈O₁₀) is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and central nervous system, etc. Over 120 plants have been found to contain this bioactive component, such as Selaginellaceae, Cupressaceae, Euphorbiaceae, Podocarpaceae, and Calophyllaceae plant families. This review paper aims to profile amentoflavone on its plant sources, natural derivatives, pharmacology, and pharmacokinetics, and to highlight some existing issues and perspectives in the future. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 402 KiB

Open AccessReview

Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

by Maria Pantelidou¹, Karyofyllis Tsiakitzis², Eleni A. Rekka² and Panos N. Kourounakis^1,2,*

¹ Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus

² Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece

Molecules 2017, 22(2), 307; https://doi.org/10.3390/molecules22020307 - 17 Feb 2017

Cited by 5 | Viewed by 5790

Abstract

Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation [...] Read more.

Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems) and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism. Full article

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

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20 pages, 1828 KiB

Open AccessReview

Design of Drug Delivery Systems Containing Artemisinin and Its Derivatives

by Blessing Atim Aderibigbe

Department of Chemistry, University of Fort Hare, Alice Campus, Eastern Cape 5700, South Africa

Molecules 2017, 22(2), 323; https://doi.org/10.3390/molecules22020323 - 20 Feb 2017

Cited by 57 | Viewed by 10429

Abstract

Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically [...] Read more.

Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials. In order to enhance their therapeutic efficacy, they are incorporated onto different drug delivery systems, thus yielding improved biological outcomes. This review article is focused on the currently synthesized derivatives of artemisinin and different delivery systems used for the incorporation of artemisinin and its derivatives. Full article

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

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23 pages, 873 KiB

Open AccessReview

Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors

by Damian Bartuzi^1,*, Agnieszka A. Kaczor^1,2, Katarzyna M. Targowska-Duda³ and Dariusz Matosiuk¹

¹ Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling Lab, Medical University of Lublin, 4A Chodźki Str., PL20093 Lublin, Poland

² School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland

³ Department of Biopharmacy, Medical University of Lublin, 4A Chodźki Str., PL20093 Lublin, Poland

Molecules 2017, 22(2), 340; https://doi.org/10.3390/molecules22020340 - 22 Feb 2017

Cited by 61 | Viewed by 10766

Abstract

The growing number of studies on G protein-coupled receptors (GPCRs) family are a source of noticeable improvement in our understanding of the functioning of these proteins. GPCRs are responsible for a vast part of signaling in vertebrates and, as such, invariably remain in [...] Read more.

The growing number of studies on G protein-coupled receptors (GPCRs) family are a source of noticeable improvement in our understanding of the functioning of these proteins. GPCRs are responsible for a vast part of signaling in vertebrates and, as such, invariably remain in the spotlight of medicinal chemistry. A deeper insight into the underlying mechanisms of interesting phenomena observed in GPCRs, such as biased signaling or allosteric modulation, can be gained with experimental and computational studies. The latter play an important role in this process, since they allow for observations on scales inaccessible for most other methods. One of the key steps in such studies is proper computational reconstruction of actual ligand-receptor or protein-protein interactions, a process called molecular docking. A number of improvements and innovative applications of this method were documented recently. In this review, we focus particularly on innovations in docking to GPCRs. Full article

(This article belongs to the Collection Molecular Docking)

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11 pages, 4707 KiB

Open AccessConference Report

Multifunctional Nanomaterials: Design, Synthesis and Application Properties

by Marisa Martinelli

and Miriam Cristina Strumia^*

Departamento de Química Orgánica (IPQA, CONICET-UNC), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina

Molecules 2017, 22(2), 243; https://doi.org/10.3390/molecules22020243 - 7 Feb 2017

Cited by 11 | Viewed by 5515

Abstract

The immense scope of variation in dendritic molecules (hyper-branching, nano-sized, hydrophobicity/hydrophilicity, rigidity/flexibility balance, etc.) and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. Dendritic-based materials are therefore viable alternatives to conventional polymers. The overall [...] Read more.

The immense scope of variation in dendritic molecules (hyper-branching, nano-sized, hydrophobicity/hydrophilicity, rigidity/flexibility balance, etc.) and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. Dendritic-based materials are therefore viable alternatives to conventional polymers. The overall aim of this work is to show the advantages of dendronization processes by presenting the synthesis and characterization of three different dendronized systems: (I) microbeads of functionalized chitosan; (II) nanostructuration of polypropylene surfaces; and (III) smart dendritic nanogels. The particular properties yielded by these systems could only be achieved thanks to the dendronization process. Full article

(This article belongs to the Special Issue Selected Papers from the 3rd Iberoamerican Symposium on Organic Chemistry (SIBEAQO-3))

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Molecules, Volume 22, Issue 2 (February 2017) – 154 articles

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