Molecules

9 pages, 1594 KiB

Open AccessArticle

New Casbane and Cembrane Diterpenoids from an Okinawan Soft Coral, Lobophytum sp.

by Prodip K. Roy^1,*, Runa Ashimine¹, Haruna Miyazato², Junsei Taira² and Katsuhiro Ueda^1,*

¹ Department of Chemistry, Biology, and Marine Science, University of the Ryukyus, 1 Senbaru, Nishihara-cho, Okinawa 903-2013, Japan

² Department of Bioresources Engineering, Okinawa National College of Technology, 905 Henoko, Nago-shi, Okinawa 905-2192, Japan

Molecules 2016, 21(5), 679; https://doi.org/10.3390/molecules21050679 - 23 May 2016

Cited by 17 | Viewed by 5840

Abstract

A new rare casbane-type diterpenoid 1 and two new cembrane diterpenoids 2, 3 were isolated from an Okinawan soft coral, Lobophytum sp., together with four known cembrane diterpenoids 4–7. Their structures were elucidated by extensive analysis of spectroscopic data (1D and 2D NMR, [...] Read more.

A new rare casbane-type diterpenoid 1 and two new cembrane diterpenoids 2, 3 were isolated from an Okinawan soft coral, Lobophytum sp., together with four known cembrane diterpenoids 4–7. Their structures were elucidated by extensive analysis of spectroscopic data (1D and 2D NMR, IR, and MS) and a molecular modeling study. The new isolates showed weak anti-bacterial activity, mild cytotoxicity against HCT116 cells, and anti-inflammatory effect in LPS/IFN-γ-stimulated RAW 264.7 macrophage cells. Full article

(This article belongs to the Section Natural Products Chemistry)

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27 pages, 1858 KiB

Open AccessArticle

Synthesis and p38 Inhibitory Activity of Some Novel Substituted N,N′-Diarylurea Derivatives

by Dianxi Zhu^1,2, Qifeng Xing², Ruiyuan Cao², Dongmei Zhao^1,* and Wu Zhong^2,*

¹ Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China

² Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd., Beijing 100850, China

Molecules 2016, 21(5), 677; https://doi.org/10.3390/molecules21050677 - 23 May 2016

Cited by 9 | Viewed by 6412

Abstract

We have identified a novel series of substituted N,N′-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were [...] Read more.

We have identified a novel series of substituted N,N′-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC₅₀ value of 0.47 nM and a KD value of 1.54 × 10⁻⁸ and appears to be the most promising one in the series. Full article

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

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14 pages, 3450 KiB

Open AccessArticle

Structure Identification and Anti-Cancer Pharmacological Prediction of Triterpenes from Ganoderma lucidum

by Yanyan Shao^1,†, Liansheng Qiao^2,†, Lingfang Wu^1,†, Xuefei Sun¹, Dan Zhu¹, Guanghui Yang¹, Xiaoxue Zhang¹, Xin Mao¹, Wenjing Chen¹, Wenyi Liang¹, Yanling Zhang^2,* and Lanzhen Zhang^1,*

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China

² Beijing Key Laboratory of TCM Foundation and New Drug Research, School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100102, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 678; https://doi.org/10.3390/molecules21050678 - 21 May 2016

Cited by 30 | Viewed by 8645

Abstract

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs [...] Read more.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3β,7β,15β-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3β,7β,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3β,7β,15α,25-tetrol (5) and (3β,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2′-hydroxypalmitoyl-l-O-β-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3β,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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21 pages, 1130 KiB

Open AccessArticle

Synthesis and in Vitro and in Vivo Anticoagulant and Antiplatelet Activities of Amidino- and Non-Amidinobenzamides

by Soo Hyun Lee^1,†, Wonhwa Lee^2,3,†, Jong-Sup Bae^2,* and Eunsook Ma^1,*

¹ College of Pharmacy, Catholic University of Daegu, Hayang-ro 13-13, Hayang-eup, Gyeongsan-si, Gyeongbuk 712-702, Korea

² College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea

³ Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422, Korea

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 676; https://doi.org/10.3390/molecules21050676 - 21 May 2016

Cited by 8 | Viewed by 6442

Abstract

Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin [...] Read more.

Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. From the aPTT results obtained, two amidinobenzamides, N-(3′-amidinophenyl)-3-(thiophen-2′′-ylcarbonylamino) benzamide (1, 33.2 ± 0.7 s) and N-(4′-amidinophenyl)-3-(thiophen-2′′-ylcarbonylamino) benzamide (2, 43.5 ± 0.6 s) were selected to investigate the further anticoagulant and antiplatelet activities. The aPTT results of 1 (33.2 ± 0.7 s) and 2 (43.5 ± 0.6 s) were compared with heparin (62.5 ± 0.8 s) in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity (ex vivo) and on tail bleeding time (in vivo) on mice. A tail cutting/bleeding time assay revealed that both 1 and 2 prolonged bleeding time in mice at a dose of 24.1 g/mouse and above. Compounds 1 and 2 dose-dependently inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In addition, 1 and 2 were evaluated on the inhibitory activities of thrombin and FXa as well as the generation of thrombin and FXa in human umbilical vein endothelial cells (HUVECs). Collectively, 1 and 2 possess some antiplatelet and anticoagulant activities and offer a basis for development of a novel antithrombotic product. Full article

(This article belongs to the Section Bioorganic Chemistry)

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15 pages, 2354 KiB

Open AccessArticle

Astragalin, a Flavonoid from Morus alba (Mulberry) Increases Endogenous Estrogen and Progesterone by Inhibiting Ovarian Granulosa Cell Apoptosis in an Aged Rat Model of Menopause

by Min Wei^1,†, Gail B. Mahady^2,†, Daniel Liu^3,*, Zhi S. Zheng¹ and Ye Lu¹

¹ Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210041, China

² Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA

³ Beijing Clinical Services Center, No. 103 Chaoyang North Road, Beijing 100123, China

^† These authors have contributed equally to this work.

Molecules 2016, 21(5), 675; https://doi.org/10.3390/molecules21050675 - 21 May 2016

Cited by 30 | Viewed by 9271

Abstract

Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using [...] Read more.

Background: To determine the mechanism by which the flavonoid glycoside astragalin (AST) reduces ovarian failure in an aged rat model of menopause. Methods: The in vivo effect of AST on granulosa cell (GC) apoptosis in aged female rats was determined using flow cytometry. In vitro, the effects of AST on cultured GCs were investigated using the MTT proliferation assay and western blot assays. Results: Aged rats had significantly higher GC apoptosis as compared with young female rats. Treatment of aged rats with AST (all three doses; p < 0.01) or Progynova (p < 0.01) significantly reduced GC apoptosis as compared with the aged controls. The proportions of total apoptotic GCs was 25.70%, 86.65%, 47.04%, 27.02%, 42.09% and 56.42% in the normal, aged, 17β-estradiol (E₂), high dose AST, medium dose AST, and low dose AST-treated groups, respectively. Significant increases of serum E₂ and P₄ levels, as well as altered levels of serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. In cultured rat GCs, AST stimulated GC proliferation, E₂ and progesterone (P₄) secretion, reduced apoptosis, reduced the level of the pro-apoptotic protein Bcl-2 (p < 0.01), but had no effect on BAX. Conclusions: AST enhanced ovarian function in aged female rats by increasing E₂ and P₄ levels, and reducing ovarian GC apoptosis via a mechanism involving Bcl-2. These data demonstrate a new pharmacological activity for AST, as well as a novel mechanism of action, and further suggest that AST may be a new therapeutic agent for the management of menopausal symptoms. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 1471 KiB

Open AccessArticle

Synthesis and Characterization of Novel Cu(II), Pd(II) and Pt(II) Complexes with 8-Ethyl-2-hydroxytricyclo(7.3.1.0^2,7)tridecan-13-one-thiosemicarbazone: Antimicrobial and in Vitro Antiproliferative Activity

by Elena Pahonțu^1,*, Codruța Paraschivescu^2,*, Diana-Carolina Ilieș³, Donald Poirier⁴

, Camelia Oprean⁵, Virgil Păunescu⁶, Aurelian Gulea⁷

, Tudor Roșu⁸ and Ovidiu Bratu⁹

¹ Inorganic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, 6 Traian Vuia Street, Bucharest 020956, Romania

² Organic Chemistry Department, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Street, Bucharest 050663, Romania

³ Organic Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy ”Carol Davila”, 6 Traian Vuia Street, Bucharest 020956, Romania

⁴ Oncology and Molecular Endocrinology Research Center CHUL, Research Center and Universite Laval, CHUQ-CHUL, 2705 Boulevard Laurier, Quebec City, QC G1V 4G2, Canada

⁵ Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy “Victor Babeş”, Timişoara 300041, Romania

⁶ Functional Sciences Department, Faculty of Medicine, University of Medicine and Pharmacy “Victor Babeş”, 2 Eftimie Murgu Square, Timişoara 300041, Romania

⁷ Coordination Chemistry Department, Moldova State University, 60 Mateevici Street, Chisinau 2009, Moldova

⁸ Inorganic Chemistry Department, Faculty of Chemistry, University of Bucharest, 23 Dumbrava Rosie Street, Bucharest 020462, Romania

⁹ Clinic of Urology, Universitary Emergency Central Military Hospital, Clinical Departament 3, University of Medicine and Pharmacy “Carol Davila”, 6 Traian Vuia Street, Bucharest 020956, Romania

Molecules 2016, 21(5), 674; https://doi.org/10.3390/molecules21050674 - 21 May 2016

Cited by 53 | Viewed by 7429

Abstract

New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H₂O)₂(OAc)) (1), (Cu(HL)(H₂O)₂(SO₄)) (2), (Cu(L)(H₂O)₂(NO₃)) (3), (Cu(L)(H₂O)₂(ClO₄)) (4 [...] Read more.

New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H₂O)₂(OAc)) (1), (Cu(HL)(H₂O)₂(SO₄)) (2), (Cu(L)(H₂O)₂(NO₃)) (3), (Cu(L)(H₂O)₂(ClO₄)) (4), (Cu(L)₂(H₂O)₂) (5), (Pd(L)(OAc))H₂O (6), and (Pt(L)₂) (7) were synthesized from 8-ethyl-2-hydroxytricyclo(7.3.1.0^2,7)tridecan-13-one thiosemicarbazone (HL). The ligand and its metal complexes were characterized by IR, ¹H-NMR, ¹³C-NMR, UV-Vis, FAB, EPR, mass spectroscopy, elemental and thermal analysis, magnetic susceptibility measurements and molar electric conductivity. The free ligand and the metal complexes have been tested for their antimicrobial activity against E. coli, S. enteritidis, S. aureus, E. faecalis, C. albicans and cytotoxicity against the NCI-H1573 lung adenocarcinoma, SKBR-3 human breast, MCF-7 human breast, A375 human melanoma and HL-60 human promyelocytic leukemia cell lines. Copper complex 2 exhibited the best antiproliferative activities against MCF-7 human breast cancer cells. A significant inhibition of malignant HL-60 cell growth was observed for copper complex 2, palladium complex 6 and platinum complex 7, with IC₅₀ values of 1.6 µM, 6.5 µM and 6.4 µM, respectively. Full article

(This article belongs to the Special Issue ECSOC-19)

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1 pages, 144 KiB

Open AccessCorrection

Correction: Xiang, S., et al. Schisandrin B Induces Apoptosis and Cell Cycle Arrest of Gallbladder Cancer Cells. Molecules 2014, 19, 13235–13250

by Shan-Shan Xiang^1,2,3,†, Xu-An Wang^1,2,3,†, Huai-Feng Li^1,2,3,†, Yi-Jun Shu^1,2,3, Run-Fa Bao^1,2,3, Fei Zhang^1,2,3, Yang Cao^1,2,3, Yuan-Yuan Ye^1,2,3, Hao Weng^1,2,3, Wen-Guang Wu^1,2,3, Jia-Sheng Mu^1,2,3, Xiang-Song Wu^1,2,3, Mao-Lan Li^1,2,3, Yun-Ping Hu^1,2,3, Lin Jiang^1,2,3, Zhu-Jun Tan^1,2,3, Wei Lu^1,2,3, Feng Liu^4,* and Ying-Bin Liu^1,2,3,*

¹ Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China

² Laboratory of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China

³ Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, No. 227 South Chongqing Road, Shanghai 200025, China

⁴ The First Affiliated Hospital Nanchang University Emergency Unit, No. 17 Yongwai Road, Nanchang 330006, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 673; https://doi.org/10.3390/molecules21050673 - 20 May 2016

Cited by 1 | Viewed by 4400

Abstract

We would like to change the Affiliation addresses on Page 13235 of paper [1], [...] Full article

(This article belongs to the Section Natural Products Chemistry)

12 pages, 2328 KiB

Open AccessArticle

Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs

by Kyeong-Ok Choi, Jaehyeog Choe, Seokjin Suh and Sanghoon Ko^*

Department of Food Science and Technology, Sejong University, 261 Neungdong-ro, Gwangjin-gu, Seoul 143-747, Korea

Molecules 2016, 21(5), 672; https://doi.org/10.3390/molecules21050672 - 20 May 2016

Cited by 34 | Viewed by 7321

Abstract

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility [...] Read more.

The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery. Full article

(This article belongs to the Collection Poorly Soluble Drugs)

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11 pages, 2353 KiB

Open AccessArticle

Thermal Conductivity of Epoxy Resin Composites Filled with Combustion Synthesized h-BN Particles

by Shyan-Lung Chung^1,2,* and Jeng-Shung Lin²

¹ Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan 70101, Taiwan

² Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan

Molecules 2016, 21(5), 670; https://doi.org/10.3390/molecules21050670 - 20 May 2016

Cited by 99 | Viewed by 11941

Abstract

The thermal conductivity of epoxy resin composites filled with combustion-synthesized hexagonal boron nitride (h-BN) particles was investigated. The mixing of the composite constituents was carried out by either a dry method (involving no use of solvent) for low filler loadings or a solvent [...] Read more.

The thermal conductivity of epoxy resin composites filled with combustion-synthesized hexagonal boron nitride (h-BN) particles was investigated. The mixing of the composite constituents was carried out by either a dry method (involving no use of solvent) for low filler loadings or a solvent method (using acetone as solvent) for higher filler loadings. It was found that surface treatment of the h-BN particles using the silane 3-glycidoxypropyltrimethoxysilane (GPTMS) increases the thermal conductivity of the resultant composites in a lesser amount compared to the values reported by other studies. This was explained by the fact that the combustion synthesized h-BN particles contain less –OH or active sites on the surface, thus adsorbing less amounts of GPTMS. However, the thermal conductivity of the composites filled with the combustion synthesized h-BN was found to be comparable to that with commercially available h-BN reported in other studies. The thermal conductivity of the composites was found to be higher when larger h-BN particles were used. The thermal conductivity was also found to increase with increasing filler content to a maximum and then begin to decrease with further increases in this content. In addition to the effect of higher porosity at higher filler contents, more horizontally oriented h-BN particles formed at higher filler loadings (perhaps due to pressing during formation of the composites) were suggested to be a factor causing this decrease of the thermal conductivity. The measured thermal conductivities were compared to theoretical predictions based on the Nielsen and Lewis theory. The theoretical predictions were found to be lower than the experimental values at low filler contents (< 60 vol %) and became increasing higher than the experimental values at high filler contents (> 60 vol %). Full article

(This article belongs to the Special Issue Boron Nitride: Synthesis and Application)

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9 pages, 941 KiB

Open AccessArticle

Anti-Inflammatory Oleanolic Triterpenes from Chinese Acorns

by Jie Huang¹, Yihai Wang¹, Chuan Li¹, Xinluan Wang² and Xiangjiu He^1,*

¹ School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

² Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

Molecules 2016, 21(5), 669; https://doi.org/10.3390/molecules21050669 - 20 May 2016

Cited by 23 | Viewed by 6815

Abstract

Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata). [...] Read more.

Acorns play an important role in human history and are a source of food and recipes for many cultures around the world. In this study, eleven oleanolic triterpenes, one of which was novel, were isolated from Chinese acorns (Quercus serrata var. brevipetiolata). The chemical structure of the novel triterpene, which was identified as 2α,3β,19α-trihydroxy-24-oxo-olean-12-en-28-oic acid (1), was established based on the interpretation of chemical and spectroscopic analyses, including IR, HR-ESI-MS, and NMR experiments (¹H, ¹³C NMR, DEPT, ¹H-¹H COSY, HSQC, HMBC, and NOESY). All isolated compounds were tested for their inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compared with the positive control drug indomethacin (IC₅₀ = 47.4 μM), compounds 1, 3, 6 and 8 exhibited remarkable anti-inflammatory activities with IC₅₀ values of 5.4, 7.8, 4.0 and 8.9 μM, respectively. Besides, compounds 2, 4, 7 and 9 also showed moderate anti-inflammatory activities with IC₅₀ values of 10.1, 13.0, 20.1 and 17.2 μM, respectively. Furthermore, Compound 1 could inhibit TNF-α-induced IL-6 and IL-8 production in MH7A cells. Full article

(This article belongs to the Collection Triterpenes and Triterpenoids)

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12 pages, 3889 KiB

Open AccessArticle

Gold Incorporated Mesoporous Silica Thin Film Model Surface as a Robust SERS and Catalytically Active Substrate

by Anandakumari Chandrasekharan Sunil Sekhar^1,2,* and Chathakudath Prabhakaran Vinod^1,2,3,*

¹ Catalysis Division, CSIR-National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008, India

² Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2, Rafi Marg, New Delhi 110 001, India

³ Center of Excellence on Surface Science, CSIR-National Chemical Laboratory, Dr Homi Bhabha Road, Pune 411 008, India

Molecules 2016, 21(5), 667; https://doi.org/10.3390/molecules21050667 - 20 May 2016

Cited by 7 | Viewed by 6760

Abstract

Ultra-small gold nanoparticles incorporated in mesoporous silica thin films with accessible pore channels perpendicular to the substrate are prepared by a modified sol-gel method. The simple and easy spin coating technique is applied here to make homogeneous thin films. The surface characterization using [...] Read more.

Ultra-small gold nanoparticles incorporated in mesoporous silica thin films with accessible pore channels perpendicular to the substrate are prepared by a modified sol-gel method. The simple and easy spin coating technique is applied here to make homogeneous thin films. The surface characterization using FESEM shows crack-free films with a perpendicular pore arrangement. The applicability of these thin films as catalysts as well as a robust SERS active substrate for model catalysis study is tested. Compared to bare silica film our gold incorporated silica, GSM-23F gave an enhancement factor of 10³ for RhB with a laser source 633 nm. The reduction reaction of p-nitrophenol with sodium borohydride from our thin films shows a decrease in peak intensity corresponding to –NO₂ group as time proceeds, confirming the catalytic activity. Such model surfaces can potentially bridge the material gap between a real catalytic system and surface science studies. Full article

(This article belongs to the Special Issue Coinage Metal (Copper, Silver, and Gold) Catalysis)

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10 pages, 2246 KiB

Open AccessReview

Flavin-Dependent Thymidylate Synthase as a New Antibiotic Target

by Michael Choi, Kalani Karunaratne and Amnon Kohen^*

Department of Chemistry, The University of Iowa, Iowa City, IA 52242-1727, USA

Molecules 2016, 21(5), 654; https://doi.org/10.3390/molecules21050654 - 20 May 2016

Cited by 23 | Viewed by 9739

Abstract

In humans de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not [...] Read more.

In humans de novo synthesis of 2′-deoxythymidine-5′-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not present in human cells. A number of pathogenic bacteria, however, depend on this enzyme in lieu of or in conjunction with the analogous human pathway. Thus, inhibitors of this enzyme may serve as antibiotics. Here, we review the similarities and differences of FDTS vs. TSase including aspects of their structure and chemical mechanism. In addition, we review current progress in the search for inhibitors of flavin dependent thymidylate synthase as potential novel therapeutics. Full article

(This article belongs to the Special Issue 20th Anniversary of Molecules—Recent Advances in Medicinal Chemistry)

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12 pages, 2327 KiB

Open AccessArticle

BiOBr/BiOI Photocatalyst Based on Fly Ash Cenospheres with Improved Photocatalytic Performance

by Li Lin^1,2,*, Manhong Huang² and Donghui Chen^2,3,*

¹ School of Chemical and Environmental Engineering, Hunan City University, Yiyang 413000, China

² School of Environmental Science and Engineering, Donghua University, Shanghai 201620, China

³ Shanghai Institute of Technology, Shanghai 200235, China

Molecules 2016, 21(5), 666; https://doi.org/10.3390/molecules21050666 - 19 May 2016

Cited by 18 | Viewed by 6566

Abstract

A series of BiOBr/BiOI photocatalysts supported on fly-ash cenospheres (FACs) were successfully prepared via a facile one-pot alcoholysis method. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectrometer (XPS) and UV-visible diffuse reflectance spectroscopy (DRS). The [...] Read more.

A series of BiOBr/BiOI photocatalysts supported on fly-ash cenospheres (FACs) were successfully prepared via a facile one-pot alcoholysis method. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectrometer (XPS) and UV-visible diffuse reflectance spectroscopy (DRS). The results indicate that pH value plays a critical role in BiOBr/BiOI loading. Based on the photodegradation tests under visible light irradiation (blue LED irradiation), the photocatalytic property of BiOBr/BiOI/FACs photocatalysts obtained under alkaline conditions is superior to that prepared under neutral or acidic conditions, and higher than those of BiOB/FACs and BiOI//FACs. The improved photocatalytic performance of BiOBr/BiOI/FACs can be attributed to more BiOBr/BiOI loaded on the surface of FACs and the efficient photogenerated electron-hole separation. Full article

(This article belongs to the Section Photochemistry)

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12 pages, 2027 KiB

Open AccessArticle

Novel Cage-Like Hexanuclear Nickel(II) Silsesquioxane. Synthesis, Structure, and Catalytic Activity in Oxidations with Peroxides

by Alexey N. Bilyachenko^1,2,*

, Alexey I. Yalymov¹, Lidia S. Shul’pina¹

, Dalmo Mandelli³, Alexander A. Korlyukov^1,4

, Anna V. Vologzhanina¹

, Marina A. Es’kova¹, Elena S. Shubina¹

, Mikhail M. Levitsky¹ and Georgiy B. Shul’pin^5,6,*

¹ Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Str. 28, 119991 Moscow, Russia

² Inorganic Chemistry Department, People’s Friendship University of Russia, Miklukho-Maklay Str. 6, 117198 Moscow, Russia

³ Center of Natural and Human Sciences, Federal University of ABC (UFABC), Santa Adélia Street, 166, Bangu, Santo André, SP 09210-170, Brazil

⁴ Chemistry Department, Russian National Research Medical University, Ostrovitianov str. 1, 117997 Moscow, Russia

⁵ Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina, dom 4, 119991 Moscow, Russia

⁶ Chair of Chemistry and Physics, Plekhanov Russian University of Economics, Stremyannyi pereulok, dom 36, 117997 Moscow, Russia

Molecules 2016, 21(5), 665; https://doi.org/10.3390/molecules21050665 - 19 May 2016

Cited by 33 | Viewed by 7450

Abstract

New hexanuclear nickel(II) silsesquioxane [(PhSiO_1.5)₁₂(NiO)₆(NaCl)] (1) was synthesized as its dioxane-benzonitrile-water complex (PhSiO_1,5)₁₂(NiO)₆(NaCl)(C₄H₈O₂)₁₃(PhCN)₂(H₂O)₂ and studied by X-ray and [...] Read more.

New hexanuclear nickel(II) silsesquioxane [(PhSiO_1.5)₁₂(NiO)₆(NaCl)] (1) was synthesized as its dioxane-benzonitrile-water complex (PhSiO_1,5)₁₂(NiO)₆(NaCl)(C₄H₈O₂)₁₃(PhCN)₂(H₂O)₂ and studied by X-ray and topological analysis. The compound exhibits cylinder-like type of molecular architecture and represents very rare case of polyhedral complexation of metallasilsesquioxane with benzonitrile. Complex 1 exhibited catalytic activity in activation of such small molecules as light alkanes and alcohols. Namely, oxidation of alcohols with tert-butylhydroperoxide and alkanes with meta-chloroperoxybenzoic acid. The oxidation of methylcyclohexane gave rise to the isomeric ketones and unusual distribution of alcohol isomers. Full article

(This article belongs to the Special Issue Metal Mediated Activation of Small Molecules)

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14 pages, 2066 KiB

Open AccessCommunication

Comprehensive Qualitative Ingredient Profiling of Chinese Herbal Formula Wu-Zhu-Yu Decoction via a Mass Defect and Fragment Filtering Approach Using High Resolution Mass Spectrometry

by Huarong Xu¹, Huibin Niu¹, Bosai He¹, Chang Cui², Qing Li¹ and Kaishun Bi^1,*

¹ National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China

² Liaoning Institute of Analytical Science, 103 Wanliutang Rd., Shenyang 110015, China

Molecules 2016, 21(5), 664; https://doi.org/10.3390/molecules21050664 - 19 May 2016

Cited by 24 | Viewed by 6716

Abstract

The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The [...] Read more.

The Wu-Zhu-Yu decoction is a traditional Chinese medicine formula for the treatment of headache. To reveal its material basis, a rapid and reliable liquid chromatography-high resolution mass spectrometry method was established for comprehensive profiling of the chemical ingredients in the Wu-Zhu-Yu decoction. The method was used on a quadrupole time-of-flight mass spectrometer along with an advanced data processing procedure consisting of mass accuracy screening, mass defect filtering and fragment filtering. After eliminating interference with a filtering approach, the MS data profiling was made more distinct and accurate. With the optimized conditions of only 35 min LC separation and single sample injection of each positive or negative ion mode, a total of 168 compounds were characterized, including 23 evodiamine and its analogous alkaloids, 12 limonoids, 17 gingerols, 38 ginsenosides, 15 flavonoids, 16 organic acids, 14 alkaloids, 5 saponins, 3 2,2-dimethylchromenes and 25 other compounds. The fragmentation patterns of representative compounds were illustrated as well. Integrative qualitative analysis of the Wu-Zhu-Yu decoction by high resolution mass spectrometry was accomplished and reported for the first time. The study demonstrated that the established method was a powerful and reliable strategy for comprehensive detection and would be widely applicable for identification of complicated components from herbal prescriptions, and may provide a basis for chemical analysis of other complex mixtures. Full article

(This article belongs to the Section Natural Products Chemistry)

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18 pages, 1704 KiB

Open AccessReview

Antiproliferative Fate of the Tetraploid Formed after Mitotic Slippage and Its Promotion; A Novel Target for Cancer Therapy Based on Microtubule Poisons

by Yuji Nakayama¹ and Toshiaki Inoue^2,3,*

¹ Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

² Division of Human Genome Science, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

³ Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

Molecules 2016, 21(5), 663; https://doi.org/10.3390/molecules21050663 - 19 May 2016

Cited by 28 | Viewed by 8604

Abstract

Microtubule poisons inhibit spindle function, leading to activation of spindle assembly checkpoint (SAC) and mitotic arrest. Cell death occurring in prolonged mitosis is the first target of microtubule poisons in cancer therapies. However, even in the presence of microtubule poisons, SAC and mitotic [...] Read more.

Microtubule poisons inhibit spindle function, leading to activation of spindle assembly checkpoint (SAC) and mitotic arrest. Cell death occurring in prolonged mitosis is the first target of microtubule poisons in cancer therapies. However, even in the presence of microtubule poisons, SAC and mitotic arrest are not permanent, and the surviving cells exit the mitosis without cytokinesis (mitotic slippage), becoming tetraploid. Another target of microtubule poisons-based cancer therapy is antiproliferative fate after mitotic slippage. The ultimate goal of both the microtubule poisons-based cancer therapies involves the induction of a mechanism defined as mitotic catastrophe, which is a bona fide intrinsic oncosuppressive mechanism that senses mitotic failure and responds by driving a cell to an irreversible antiproliferative fate of death or senescence. This mechanism of antiproliferative fate after mitotic slippage is not as well understood. We provide an overview of mitotic catastrophe, and explain new insights underscoring a causal association between basal autophagy levels and antiproliferative fate after mitotic slippage, and propose possible improved strategies. Additionally, we discuss nuclear alterations characterizing the mitotic catastrophe (micronuclei, multinuclei) after mitotic slippage, and a possible new type of nuclear alteration (clustered micronuclei). Full article

(This article belongs to the Special Issue New Generation of Microtubule-Interacting Anticancer Agents)

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11 pages, 2656 KiB

Open AccessArticle

Adsorption and Gas Separation of Molecules by Carbon Nanohorns

by Silvina M. Gatica^1,*, Anton Nekhai^2,† and Adam Scrivener^3,‡

¹ Department of Physics and Astronomy, Howard University, 2355 Sixth Street NW, Washington, DC 20059, USA

² Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, USA

³ Department of Computer Science, University of Rochester, 500 Joseph C. Wilson Boulevard, Rochester, NY 14627, USA

^† Participant in the summer Research Experiences for Undergraduates (REU), National Science Foundation (NSF) summer program, at Howard University (2015)

^‡ Participant in the summer Research Experiences for Undergraduates (REU), National Science Foundation (NSF) summer program, at Howard University (2014)

Molecules 2016, 21(5), 662; https://doi.org/10.3390/molecules21050662 - 19 May 2016

Cited by 10 | Viewed by 5173

Abstract

In this paper, we report the results of Monte Carlo simulations of the adsorption of neon, argon, methane and carbon dioxide in carbon nanohorns. We model the nanohorns as an array of carbon cones and obtained adsorption isotherms and isosteric heats. The main [...] Read more.

In this paper, we report the results of Monte Carlo simulations of the adsorption of neon, argon, methane and carbon dioxide in carbon nanohorns. We model the nanohorns as an array of carbon cones and obtained adsorption isotherms and isosteric heats. The main sites of adsorption are inside the cones and in the interstices between three cones. We also calculated the selectivity of carbon dioxide/methane, finding that nanohorns are a suitable substrate for gas separation. Our simulations are compared to available experimental data. Full article

(This article belongs to the Special Issue Carbon Nanotubes: Advances and Applications)

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13 pages, 851 KiB

Open AccessArticle

Synthesis of Novel Symmetrical 1,4-Disubstituted 1,2,3-Bistriazole Derivatives via ‘Click Chemistry’ and Their Biological Evaluation

by Esra Düğdü^1,*, Dilek Ünlüer¹, Fatih Çelik¹, Kemal Sancak¹, Şengül Alpay Karaoğlu²

and Arzu Özel³

¹ Department of Chemistry, Karadeniz Technical University, Trabzon 61080, Turkey

² Department of Biology, Recep Tayyip Erdoğan University, Rize 53100, Turkey

³ Faculty of Pharmacy, Karadeniz Technical University, Trabzon 61080, Turkey

Molecules 2016, 21(5), 659; https://doi.org/10.3390/molecules21050659 - 19 May 2016

Cited by 13 | Viewed by 5435

Abstract

A series of symmetric bis-1,2,3-triazole compounds 2–5(a–f) were synthesized as potential antioxidant agents via click chemistry. Their structures were confirmed by ¹H-NMR and ¹³C-NMR. All of the synthesized compounds were subjected to antioxidant and antimicrobial assays. The antioxidant activity of these [...] Read more.

A series of symmetric bis-1,2,3-triazole compounds 2–5(a–f) were synthesized as potential antioxidant agents via click chemistry. Their structures were confirmed by ¹H-NMR and ¹³C-NMR. All of the synthesized compounds were subjected to antioxidant and antimicrobial assays. The antioxidant activity of these compounds (AChE inhibition, DPPH and SOD activities) was evaluated. Compound 2f was found to show the highest AChE inhibition activity of all compounds, while compound 3b showed a strong inhibitory effect on DPPH radical and compound 2a was the most effective of all compounds for SOD activity. All synthesized compounds were found to possess moderate antibacterial activity against the bacteria E. coli and Y.pseudotuberculosis. Full article

(This article belongs to the Section Organic Chemistry)

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13 pages, 2442 KiB

Open AccessArticle

Design, Synthesis and Structure-Activity Relationships of Novel Chalcone-1,2,3-triazole-azole Derivates as Antiproliferative Agents

by Sai-Yang Zhang^1,†, Dong-Jun Fu^1,†, Xiao-Xin Yue², Ying-Chao Liu¹, Jian Song¹, Hui-Hui Sun¹, Hong-Min Liu^1,* and Yan-Bing Zhang^1,*

¹ Collaborative Innovation Center of New Drug Research and Safety Evaluation, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China

² Henan Medical College, Zhengzhou 451191, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 653; https://doi.org/10.3390/molecules21050653 - 19 May 2016

Cited by 58 | Viewed by 8913

Abstract

A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, [...] Read more.

A series of novel chalcone-1,2,3-triazole-azole hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, EC-109 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound I-21 showed the most excellent antiproliferative activity with an IC₅₀ value of 1.52 μM against SK-N-SH cancer cells. Further mechanism studies revealed that compound I-21 induced morphological changes of SK-N-SH cancer cells possibly by inducing apoptosis. Novel chalcone-1,2,3-triazole-azole derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating neuroblastoma. 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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36 pages, 4347 KiB

Open AccessReview

Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

by Susann Schröder

, Barbara Wenzel, Winnie Deuther-Conrad

, Matthias Scheunemann and Peter Brust^*

Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Permoserstraße 15, Leipzig 04318, Germany

Molecules 2016, 21(5), 650; https://doi.org/10.3390/molecules21050650 - 19 May 2016

Cited by 21 | Viewed by 6953

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition [...] Read more.

Cyclic nucleotide phosphodiesterases (PDEs) are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET) in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-)clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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12 pages, 2816 KiB

Open AccessArticle

Effects of Resveratrol Supplementation and Exercise Training on Exercise Performance in Middle-Aged Mice

by Nai-Wen Kan¹, Chin-Shan Ho², Yen-Shuo Chiu^2,3,4, Wen-Ching Huang², Pei-Yu Chen², Yu-Tang Tung^2,* and Chi-Chang Huang^2,*

¹ Center for Liberal Arts, Taipei Medical University, Taipei 11031, Taiwan

² Graduate Institute of Sports Science, National Taiwan Sport University, 250 Wenhua 1st Rd., Guishan Township, Taoyuan County 33301, Taiwan

³ Department of Orthopedic Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan

⁴ School of Nutrition and Health Sciences, Taipei Medical University, Taipei City 11031, Taiwan

Molecules 2016, 21(5), 661; https://doi.org/10.3390/molecules21050661 - 18 May 2016

Cited by 53 | Viewed by 8856

Abstract

Resveratrol (RES) has antioxidative, anti-inflammatory, anticancer, antidiabetic, antiasthmatic, antalgic, and anti-fatigue activities. Exercise training (ET) improves frailty resulting from aging. This study evaluated the effects of a combination of RES supplementation and ET on the exercise performance of aged mice. C57BL/6J mice (16 [...] Read more.

Resveratrol (RES) has antioxidative, anti-inflammatory, anticancer, antidiabetic, antiasthmatic, antalgic, and anti-fatigue activities. Exercise training (ET) improves frailty resulting from aging. This study evaluated the effects of a combination of RES supplementation and ET on the exercise performance of aged mice. C57BL/6J mice (16 months old) were randomly divided into four groups: an older control group (OC group), supplementation with RES group (RES group), ET group (ET group), and a combination of ET and RES supplementation group (ET+RES group). Other 10-week-old mice were used as a young control group (Y-Ctrl group). In this study, exercise performance was evaluated using forelimb grip strength and exhaustive swimming time, as well as levels of plasma lactate, ammonia, glucose, and creatine kinase after an acute swimming exercise. Our results showed that the forelimb grip strength of mice in the ET+RES group was significantly higher than those in the OC, RES, and ET groups (by 1.3-, 1.2-, and 1.1-fold, respectively, p < 0.05), and exhibited no difference with the Y-Ctrl group. The endurance swimming test showed that swimming times of the ET and ET+RES groups were significantly longer than those of the OC and RES groups. Moreover, plasma lactate and ammonia levels of the ET + RES group after acute swimming exercise were significantly lower compared to the OC group (p < 0.05). Thus, it was suggested that by combining RES supplementation with ET for 4 weeks, the muscle strength and endurance performance of aged mice were significantly improved compared to the single intervention with either RES or ET alone. This combination might help shorten the extent of deterioration accompanying the aging process. Full article

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

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25 pages, 3768 KiB

Open AccessReview

Synthetic Strategies for 5- and 6-Membered Ring Azaheterocycles Facilitated by Iminyl Radicals

by John C. Walton

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

Molecules 2016, 21(5), 660; https://doi.org/10.3390/molecules21050660 - 18 May 2016

Cited by 56 | Viewed by 10468

Abstract

The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a comparatively small number of ring-containing structures. Pyrrole, indole, pyridine, quinoline, quinazoline and related 6-membered ring-containing aza-arenes [...] Read more.

The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a comparatively small number of ring-containing structures. Pyrrole, indole, pyridine, quinoline, quinazoline and related 6-membered ring-containing aza-arenes figure prominently. This review focuses on the search for fast, efficient and environmentally friendly preparative methods for these rings with specific emphasis on iminyl radical-mediated procedures. Oxime derivatives, particularly oxime esters and oxime ethers, are attractive precursors for these radicals. Their use is described in conventional thermolytic, microwave-assisted and UV-vis based preparative procedures. Photoredox-catalyzed protocols involving designer oxime ethers are also covered. Choice can be made amongst these synthetic strategies for a wide variety of 5- and 6-membered ring heterocycles including phenanthridine and related aza-arenes. Applications to selected natural products and bioactive molecules, including trispheridine, vasconine, luotonin A and rutaecarpine, are included. Full article

(This article belongs to the Special Issue Free Radicals in Organic Synthesis)

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5 pages, 786 KiB

Open AccessCommunication

Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells

by Tamás Horváth^1,2, Csilla Bartos¹, Alexandra Bocsik^1,3, Lóránd Kiss^1,3

, Szilvia Veszelka³, Mária A. Deli³, Gabriella Újhelyi¹, Piroska Szabó-Révész¹ and Rita Ambrus^1,*

¹ Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, Szeged H-6720, Hungary

² Goodwill Pharma Ltd., Cserzy Mihály u. 32, Szeged H-6724, Hungary

³ Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári körút 62, Szeged H-6726, Hungary

Molecules 2016, 21(5), 658; https://doi.org/10.3390/molecules21050658 - 18 May 2016

Cited by 17 | Viewed by 6819

Abstract

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need [...] Read more.

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations. Full article

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

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19 pages, 1984 KiB

Open AccessArticle

Towards a Rational Design of a Continuous-Flow Method for the Acetalization of Crude Glycerol: Scope and Limitations of Commercial Amberlyst 36 and AlF₃·3H₂O as Model Catalysts

by Sandro Guidi, Marco Noè

, Pietro Riello, Alvise Perosa and Maurizio Selva^*

Department of Molecular Sciences and Nanosystems, Centre for Sustainable Technologies, Ca’ Foscari University of Venice, Via Torino 155, 30175 Venezia Mestre, Italy

Molecules 2016, 21(5), 657; https://doi.org/10.3390/molecules21050657 - 18 May 2016

Cited by 28 | Viewed by 8919

Abstract

The acetalization of six different types of glycerol including pure, wet, and crude-like grade compounds of compositions simulating those of crude glycerols produced by the biodiesel manufacture, was carried out with two model ketones such as acetone and 2-butanone. The reaction was investigated [...] Read more.

The acetalization of six different types of glycerol including pure, wet, and crude-like grade compounds of compositions simulating those of crude glycerols produced by the biodiesel manufacture, was carried out with two model ketones such as acetone and 2-butanone. The reaction was investigated under continuous-flow (CF) conditions through a comparative analysis of an already known acetalization catalyst such as Amberlyst 36 (A36), and aluminum fluoride three hydrate (AlF₃·3H₂O, AF) whose use was never previously reported for the synthesis of acetals. At 10 bar and 25 °C, A36 was a highly active catalyst allowing good-to-excellent conversion (85%–97%) and selectivity (99%) when either pure or wet glycerol was used as a reagent. This catalyst however, proved unsuitable for the CF acetalization of crude-like glycerol (CG) since it severely and irreversibly deactivated in a few hours by the presence of low amounts of NaCl (2.5 wt %) which is a typical inorganic impurity of raw glycerol from the biorefinery. Higher temperature and pressure (up to 100 °C and 30 bar) were not successful to improve the outcome. By contrast, at 10 bar and 100 °C, AF catalyzed the acetalization of CG with both acetone and 2-butanone, yielding stable conversion and productivity up to 78% and 5.6 h⁻¹, respectively. A XRD analysis of fresh and used catalysts proved that the active phase was a solid solution (SS) of formula Al₂[F_1-x(OH)_x]₆(H₂O)_y present as a component of the investigated commercial AF sample. A hypothesis to explain the role of such SS phase was then formulated based on the Brønsted acidity of OH groups of the solid framework. Overall, the AF catalyst allowed not only a straightforward upgrading of CG to acetals, but also a more cost-efficient protocol avoiding the expensive refining of raw glycerol itself. Full article

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

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12 pages, 791 KiB

Open AccessArticle

Synthesis and Antioxidant Activity of Alkyl Nitroderivatives of Hydroxytyrosol

by Elena Gallardo^1,2, Rocío Palma-Valdés¹, Beatriz Sarriá², Irene Gallardo¹, José P. De la Cruz³, Laura Bravo², Raquel Mateos^2,* and José L. Espartero^1,*

¹ Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain

² Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), 28040 Madrid, Spain

³ Department of Pharmacology, Faculty of Medicine, University of Malaga, 29071 Malaga, Spain

Molecules 2016, 21(5), 656; https://doi.org/10.3390/molecules21050656 - 18 May 2016

Cited by 25 | Viewed by 6213

Abstract

A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT), the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson’s disease. In this work, the antioxidant activity of these novel [...] Read more.

A series of alkyl nitrohydroxytyrosyl ether derivatives has been synthesized from free hydroxytyrosol (HT), the natural olive oil phenol, in order to increase the assortment of compounds with potential neuroprotective activity in Parkinson’s disease. In this work, the antioxidant activity of these novel compounds has been evaluated using Ferric Reducing Antioxidant Power (FRAP), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and Oxygen Radical Scavenging Capacity (ORAC) assays compared to that of nitrohydroxytyrosol (NO₂HT) and free HT. New compounds showed variable antioxidant activity depending on the alkyl side chain length; compounds with short chains (2–4 carbon atoms) maintained or even improved the antioxidant activity compared to NO₂HT and/or HT, whereas those with longer side chains (6–8 carbon atoms) showed lower activity than NO₂HT but higher than HT. Full article

(This article belongs to the Section Medicinal Chemistry)

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13 pages, 2301 KiB

Open AccessArticle

Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

by Jing Hu

, Wenfang Zhao, Kehai Liu^*, Qian Yu, Yuan Mao, Zeyu Lu, Yaguang Zhang and Manman Zhu

Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China

Molecules 2016, 21(5), 655; https://doi.org/10.3390/molecules21050655 - 18 May 2016

Cited by 16 | Viewed by 6741

Abstract

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting [...] Read more.

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100–280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector. Full article

(This article belongs to the Special Issue Biomolecules Modification)

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14 pages, 3518 KiB

Open AccessArticle

Simultaneous Qualitative and Quantitative Analysis of Multiple Chemical Constituents in YiQiFuMai Injection by Ultra-Fast Liquid Chromatography Coupled with Ion Trap Time-of-Flight Mass Spectrometry

by Chunhua Liu^1,†

, Aichun Ju^2,†, Dazheng Zhou², Dekun Li², Junping Kou¹, Boyang Yu^1,3,*

and Jin Qi^1,*

¹ Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, China

² Department of Technology Development, TianJin Tasly Pride Pharmaceutical Co., Ltd., Tianjin 300410, China

³ State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 640; https://doi.org/10.3390/molecules21050640 - 18 May 2016

Cited by 28 | Viewed by 6849

Abstract

YiQiFuMai injection (YQFM) is a modern lyophilized powder preparation derived from the traditional Chinese medicine Sheng-mai san (SMS) used for treating cardiovascular diseases, such as chronic heart failure. However, its chemical composition has not been fully elucidated, particularly for the preparation derived from [...] Read more.

YiQiFuMai injection (YQFM) is a modern lyophilized powder preparation derived from the traditional Chinese medicine Sheng-mai san (SMS) used for treating cardiovascular diseases, such as chronic heart failure. However, its chemical composition has not been fully elucidated, particularly for the preparation derived from Ophiopogon japonicus. This study aimed to establish a systematic and reliable method to quickly and simultaneously analyze the chemical constituents in YQFM by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS). Sixty-five compounds in YQFM were tentatively identified by comparison with reference substances or literature data. Furthermore, twenty-one compounds, including three ophiopogonins, fifteen ginsenosides and three lignans were quantified by UFLC-IT-TOF/MS. Notably, this is the first determination of steroidal saponins from O. japonicus in YQFM. The relative standard deviations (RSDs) of intra- and inter-day precision, reproducibility and stability were <4.9% and all analytes showed good linearity (R² ≥ 0.9952) and acceptable recovery of 91.8%–104.2% (RSD ≤ 5.4%), indicating that the methods were reliable. These methods were successfully applied to quantitative analysis of ten batches of YQFM. The developed approach can provide useful and comprehensive information for quality control, further mechanistic studies in vivo and clinical application of YQFM. Full article

(This article belongs to the Section Natural Products Chemistry)

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20 pages, 1163 KiB

Open AccessArticle

Developing an Absorption–Based Quality Control Method for Hu–Gan–Kang–Yuan Capsules by UFLC–QTOF–MS/MS Screening and HPLC–DAD Quantitative Determination

by Fenghuan Wei^*, Minting Chen, Chaohua Luo, Feilong Chen, Qun Shen and Zhixian Mo

College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

Molecules 2016, 21(5), 592; https://doi.org/10.3390/molecules21050592 - 18 May 2016

Cited by 14 | Viewed by 6433

Abstract

Traditional Chinese Medicine Preparations (TCMPs) contain massive numbers of ingredients responsible for their multiple efficacies. An absorption–based quality control method for complicated TCMPs using Hu–gan–kang–yuan Capsule (HGKYC) as an example was developed. To select proper chemical markers for quality control of HGKYC, an [...] Read more.

Traditional Chinese Medicine Preparations (TCMPs) contain massive numbers of ingredients responsible for their multiple efficacies. An absorption–based quality control method for complicated TCMPs using Hu–gan–kang–yuan Capsule (HGKYC) as an example was developed. To select proper chemical markers for quality control of HGKYC, an ultra–fast liquid chromatography (UFLC) coupled with electrospray ionization quadrupole time–off light mass spectrometry (UFLC–QTOF–MS/MS) method was used for the rapid separation and structural identification of the constituents in the HGKYC extract and the rat serum after oral administration of HGKYC. As a result, one hundred and seven prototype constituents including flavonoids, organic acid, phenylpropanoids, anthraquinones, saponins, alkaloids, terpenes, phenols and amino acids in HGKYC extract, and 43 compounds found in rat serum after oral administration of HGKYC were unambiguously identified or tentatively characterized by comparing retention times and MS information with those of authentic standards or available literature references. Finally, a simple, low–cost and effective method of simultaneous determination for baicalein, wogonin, paeonol and emodin in HGKYC was developed using high performance liquid chromatography coupled with a diode array detector. In conclusion, an absorption–based quality control pattern was developed and successfully used for evaluating HGKYC. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 3869 KiB

Open AccessReview

MRI Reporter Genes for Noninvasive Molecular Imaging

by Caixia Yang^†, Rui Tian^†, Ting Liu and Gang Liu^*

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China

^† These authors contributed equally to this work.

Molecules 2016, 21(5), 580; https://doi.org/10.3390/molecules21050580 - 18 May 2016

Cited by 37 | Viewed by 9704

Abstract

Magnetic resonance imaging (MRI) is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific [...] Read more.

Magnetic resonance imaging (MRI) is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase), the receptor on the cells (e.g., transferrin receptor), and endogenous reporter genes (e.g., ferritin reporter gene). However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies. Full article

(This article belongs to the Special Issue Molecular Imaging Probes)

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10 pages, 1382 KiB

Open AccessReview

Taxanes in the Treatment of Advanced Gastric Cancer

by Byung Woog Kang¹, Oh-Kyoung Kwon², Ho Young Chung², Wansik Yu² and Jong Gwang Kim^1,*

¹ Department of Oncology/Hematology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Kyungpook National University Cancer Research Institute, 807 Hogukno, buk-gu, Daegu 41404, Korea

² Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu 41494, Korea

Molecules 2016, 21(5), 651; https://doi.org/10.3390/molecules21050651 - 17 May 2016

Cited by 18 | Viewed by 6407

Abstract

Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit [...] Read more.

Although rapid advances in treatment options have improved the prognosis of advanced gastric cancer (AGC), it remains a major public health problem and the second leading cause of cancer-related deaths in the world. Taxanes (paclitaxel and docetaxel) are microtubule stabilizing agents that inhibit the process of cell division, and have shown antitumor activity in the treatment of AGC as a single or combination chemotherapy. Accordingly, this review focuses on the efficacy and tolerability of taxanes in the first- or second-line chemotherapy setting for AGC. Full article

(This article belongs to the Special Issue New Generation of Microtubule-Interacting Anticancer Agents)

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Molecules, Volume 21, Issue 5 (May 2016) – 139 articles

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