TY  - JOUR
A1  - Bentley, T. W.
A1  - Christl, Manfred
A1  - Kemmer, R.
A1  - Llewellyn, G.
A1  - Oakley, J. E.
T1  - Kinetic and Spectroscopic Characterisation of Highly Reactive Methanesulfonates. Leaving Group Effects for Solvolyses and Comments on Geminal Electronic Effects Influencing S\(_N\)1 Reactivity
N2  - Highly reactive methanesulfonates (mesylates, ROMs) have been prepared from 1-phenylethanol. cyclohex-2-en-1-ol, diphenylmethanol and p-methoxybenzyl alcohol by treatment with methanesulfonyl chloride and triethylamine in dichloro- or trichloro-methane at - 20 to 0 °C. The mesylates. characterised in solution by \(^1\)H and \(^{13}\)C NMR at -20 °C, were obtained in satisfactory purity (ca. 95%) in cold solutions but they decomposed by reaction with chloride, triethylamine or the parent alcohol. Rate constants for solvolyses in aqueous acetone and aqueous ethanol have been determined by a fast response conductimetric method. Product selectivities for solvolyses of pmethoxybenzyl mesylate in aqueous ethanol and methanol at 0 °C have been determined by HPLC. From additional new or Iiterature kinetic data for solvolyses of corresponding bromides. chlorides and p-nitrobenzoates (OPNB). Br/CI. OMs/Br and OMs/OPNB rate ratios were calculated; the results are consistent with electronic effects stabilising the carbocationic transition states and increasing OMs/Br rate ratios for these SN 1 solvolyses; none of the evidence supports a geminal electronic effect on Br/CI rate ratios (e.g. caused by stabilisation of the initial state in pmethoxybenzyl chloride). Steric effects on ester /halide rate ratios for solvolyses of tertiary substrates are confirmed. Relative rates over a 10\(^{16}\) range for ester and halide leaving groups are evaluated for solvolyses of 1-phenylethyl substrates in 80% ethanol-water. updating previous work by Noyce et al. (1972).
KW  - Organische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-58748
ER  - 
TY  - JOUR
A1  - Becam, Jérôme
A1  - Walter, Tim
A1  - Burgert, Anne
A1  - Schlegel, Jan
A1  - Sauer, Markus
A1  - Seibel, Jürgen
A1  - Schubert-Unkmeir, Alexandra
T1  - Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria
JF  - Scientific Reports
N2  - Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.
KW  - ceramide analogs
KW  - Neisseria
KW  - ceramide
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159367
VL  - 7
ER  - 
TY  - JOUR
A1  - Bast, K.
A1  - Christl, Manfred
A1  - Huisgen, R.
A1  - Sustmann, R.
T1  - Zur Anlagerung des Benzonitriloxids an α,β-ungesättigte Carbonsäureester
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1973
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57912
ER  - 
TY  - JOUR
A1  - Bast, K.
A1  - Christl, Manfred
A1  - Huisgen, R.
A1  - Mack, W.
A1  - Sustmann, R.
T1  - Additionen des Benzonitriloxids an olefinische und acetylenische Dipolarophile
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1973
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57905
ER  - 
TY  - JOUR
A1  - Bast, K.
A1  - Christl, Manfred
A1  - Huisgen, R.
A1  - Mack, W.
T1  - Additionen der Nitriloxide an CN-Mehrfachbindungen
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1972
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57879
ER  - 
TY  - JOUR
A1  - Bast, K.
A1  - Christl, Manfred
A1  - Huisgen, R.
A1  - Mack, W.
T1  - Relative Dipolarophilen-Aktivitäten bei Cycloadditionen des Benzonitriloxids
N2  - No abstract available
KW  - Organische Chemie
Y1  - 1973
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-57935
ER  - 
TY  - JOUR
A1  - Altmann, Stephan
A1  - Mut, Jürgen
A1  - Wolf, Natalia
A1  - Meißner-Weigl, Jutta
A1  - Rudert, Maximilian
A1  - Jakob, Franz
A1  - Gutmann, Marcus
A1  - Lühmann, Tessa
A1  - Seibel, Jürgen
A1  - Ebert, Regina
T1  - Metabolic glycoengineering in hMSC-TERT as a model for skeletal precursors by using modified azide/alkyne monosaccharides
JF  - International Journal of Molecular Sciences
N2  - Metabolic glycoengineering enables a directed modification of cell surfaces by introducing target molecules to surface proteins displaying new features. Biochemical pathways involving glycans differ in dependence on the cell type; therefore, this technique should be tailored for the best results. We characterized metabolic glycoengineering in telomerase-immortalized human mesenchymal stromal cells (hMSC-TERT) as a model for primary hMSC, to investigate its applicability in TERT-modified cell lines. The metabolic incorporation of N-azidoacetylmannosamine (Ac\(_4\)ManNAz) and N-alkyneacetylmannosamine (Ac\(_4\)ManNAl) into the glycocalyx as a first step in the glycoengineering process revealed no adverse effects on cell viability or gene expression, and the in vitro multipotency (osteogenic and adipogenic differentiation potential) was maintained under these adapted culture conditions. In the second step, glycoengineered cells were modified with fluorescent dyes using Cu-mediated click chemistry. In these analyses, the two mannose derivatives showed superior incorporation efficiencies compared to glucose and galactose isomers. In time-dependent experiments, the incorporation of Ac\(_4\)ManNAz was detectable for up to six days while Ac\(_4\)ManNAl-derived metabolites were absent after two days. Taken together, these findings demonstrate the successful metabolic glycoengineering of immortalized hMSC resulting in transient cell surface modifications, and thus present a useful model to address different scientific questions regarding glycosylation processes in skeletal precursors.
KW  - hMSC-TERT
KW  - metabolic glycoengineering
KW  - glycocalyx
KW  - modified monosaccharides
KW  - click chemistry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259247
SN  - 1422-0067
VL  - 22
IS  - 6
ER  - 
TY  - JOUR
A1  - Abdelhameed, Reda F. A.
A1  - Habib, Eman S.
A1  - Goda, Marwa S.
A1  - Fahim, John Refaat
A1  - Hassanean, Hashem A.
A1  - Eltamany, Enas E.
A1  - Ibrahim, Amany K.
A1  - AboulMagd, Asmaa M.
A1  - Fayez, Shaimaa
A1  - Abd El-kader, Adel M.
A1  - Al-Warhi, Tarfah
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
A1  - Abdelmohsen, Usama Ramadan
T1  - Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum
JF  - Marine Drugs
N2  - Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC\(_{50}\) values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.
KW  - cytotoxic activity
KW  - ergosterol derivative
KW  - metabolic analysis
KW  - docking studies
KW  - seagrass
KW  - Thalassodendron ciliatum
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236085
VL  - 18
IS  - 7
ER  - 
TY  - JOUR
A1  - Abdelhameed, Reda F. A.
A1  - Habib, Eman S.
A1  - Eltahawy, Nermeen A.
A1  - Hassanean, Hashim A.
A1  - Ibrahim, Amany K.
A1  - Mohammed, Anber F.
A1  - Fayez, Shaimaa
A1  - Hayallah, Alaa M.
A1  - Yamada, Koji
A1  - Behery, Fathy A.
A1  - Al-Sanea, Mohammad M.
A1  - Alzarea, Sami I.
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
A1  - Abdelmohsen, Usama Ramadan
T1  - New cytotoxic natural products from the Red Sea sponge Stylissa carteri
JF  - Marine Drugs
N2  - Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract’s metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC\(_{50}\) values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC\(_{50}\) at 36.8 ± 0.16 µM for 1 and IC\(_{50}\) 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.
KW  - LC-HRESIMS
KW  - Stylissa carteri
KW  - ceramide
KW  - cerebroside
KW  - docking
KW  - cytotoxic activity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205795
SN  - 1660-3397
VL  - 18
IS  - 5
ER  - 
TY  - JOUR
A1  - Abdelhameed, Reda F. A.
A1  - Eltamany, Enas E.
A1  - Hal, Dina M.
A1  - Ibrahim, Amany K.
A1  - AboulMagd, Asmaa M.
A1  - Al-Warhi, Tarfah
A1  - Youssif, Khayrya A.
A1  - Abd El-kader, Adel M.
A1  - Hassanean, Hashim A.
A1  - Fayez, Shaimaa
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
A1  - Abdelmohsen, Usama Ramadan
T1  - New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies
JF  - Marine Drugs
N2  - Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.
KW  - LC-HRESIMS
KW  - Holothuria spinifera
KW  - cerebrosides
KW  - molecular docking
KW  - cytotoxicity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211089
SN  - 1660-3397
VL  - 18
IS  - 8
ER  -