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  - 
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  - 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  - Bringmann, Gerhard
A1  - Hartung, Thomas
A1  - Goebel, Lothar
A1  - Schupp, Olaf
A1  - Ewers, Christian L. J.
A1  - Schoener, Bernd
A1  - Zagst, Rainer
A1  - Peters, Karl
A1  - Von Schnering, Hans Georg
A1  - Burschka, Christian
T1  - Novel concepts in directed biaryl synthesis, IX:  Synthesis and structure of benzonaphthopyranones,  useful bridged model precursors for stereoselective biaryl syntheses
N2  - A practicable two-step procedure for the preparation of a series of lactone-type bridged biaryls 7 as favorable substrates for subsequent atropisomer-selective ring-opening reactions is described. Due to the efficiency of the coupling step, which tolerates even a telt·butyl group next to the biaryl axis and avoids problems of regioselectivity, a variety of differently substituted representatives is prepared. These cover a broad range of steric hindrance and thus molecular distortion. The structures are investigated mainly by NMR spectroscopy and X-ray diffraction, showing the lactones 7 to be helically distorted, depending on the size of the residues R.
KW  - Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-46635
ER  - 
TY  - JOUR
A1  - Bringmann, Gerhard
A1  - Ortmann, Thomas
A1  - Zagst, Rainer
A1  - Schoener, Bernd
A1  - Assi, Laurent Ake
A1  - Burschka, Christian
T1  - +/- Dioncophyllacine A, a naphthylisoquinoline alkaloid with a 4-methoxy substituent from the leaves of Triphyophyllum peltatum
N2  - The isolation and structure elucidation of rac-dioncophyllacine A from the leaves of Triphyophyllun peltatum, is described. Unlike all other naphthylisoquinoline alkaloids, this fully dehydrogenated representative has an additional methoxy group at C-4, the position of which is deduced from NOE results. Dioncophyllacine A has a 7,1' site of the biaryl axis, as in dioncophylline A. Its constitution is confirmed by an X-ray structure analysis, which shows that the crystalline form of this new alkaloid is racemic.
KW  - Dioncophyllaceae
KW  - Triphyophyllum peltaturn
KW  - Dioncophyllaceae leaves
KW  - (± )-dioncophyllacine A
KW  - naphthylisoquinoline alkaloids
KW  - structure elucidation
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31873
ER  - 
TY  - JOUR
A1  - Bringmann, Gerhard
A1  - Zagst, Rainer
A1  - Schöner, Bernd
A1  - Busse, Holger
A1  - Hemmerling, Martin
A1  - Burschka, Christian
T1  - Acetogenic Isoquinoline Alkaloids. XXIII. Structure of the Naphthyl Isoquinoline Alkaloid Dioncophylline A
N2  - No abstract available
KW  - Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31331
ER  - 
TY  - JOUR
A1  - Brixner, Tobias
A1  - Koch, Federico
A1  - Kullmann, Martin
A1  - Selig, Ulrike
A1  - Nuernberger, Patrick
A1  - Götz, Daniel C. G.
A1  - Bringmann, Gerhard
T1  - Coherent two-dimensional electronic spectroscopy in the Soret band of a chiral porphyrin dimer
JF  - New Journal of Physics
N2  - Using coherent two-dimensional (2D) electronic spectroscopy in fully noncollinear geometry, we observe the excitonic coupling of β,β'-linked bis[tetraphenylporphyrinato-zinc(II)] on an ultrafast timescale in the excited state. The results for two states in the Soret band originating from an excitonic splitting are explained by population transfer with approximately 100 fs from the energetically higher to the lower excitonic state. This interpretation is consistent with exemplary calculations of 2D spectra for a model four-level system with coupling.
KW  - optics
KW  - quantum optics
KW  - laser
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96139
ER  - 
TY  - JOUR
A1  - Brünnert, Daniela
A1  - Seupel, Raina
A1  - Goyal, Pankaj
A1  - Bach, Matthias
A1  - Schraud, Heike
A1  - Kirner, Stefanie
A1  - Köster, Eva
A1  - Feineis, Doris
A1  - Bargou, Ralf C.
A1  - Schlosser, Andreas
A1  - Bringmann, Gerhard
A1  - Chatterjee, Manik
T1  - Ancistrocladinium A induces apoptosis in proteasome inhibitor-resistant multiple myeloma cells: a promising therapeutic agent candidate
JF  - Pharmaceuticals
N2  - The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent.
KW  - multiple myeloma
KW  - ancistrocladinium A
KW  - naphthylisoquinoline alkaloids
KW  - proteasome inhibitor resistance
KW  - RNA splicing
KW  - cellular stress response
KW  - proteasome subunit beta type-5 (PSMB5)
KW  - activating transcription factor 4 (ATF4)
KW  - ataxia teleagiectasia mutated (ATM)
KW  - H2A histone family member X (H2AX)
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-362887
SN  - 1424-8247
VL  - 16
IS  - 8
ER  - 
TY  - CHAP
A1  - Burschka, Christian
A1  - Bringmann, Gerhard
A1  - Busse, Holger
A1  - Guessregen, Stefan
A1  - Schoener, Bernd
A1  - Zagst, Rainer
T1  - Structure and dynamics of free and metallated benzonaphthopyranones and -pyrans
N2  - First calculations of the structures of metal-free and complexed biaryl lactones and their confrrmation by X-ray crystaIlography, the search for the transition states of their heIimerization processes, and the spectroscopic determination of the heIimerization barriers of related cyclic ethers by DNMR are reported.
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-46858
ER  - 
TY  - JOUR
A1  - Eltamany, Enas E.
A1  - Abdelmohsen, Usama Ramadan
A1  - Hal, Dina M.
A1  - Ibrahim, Amany K.
A1  - Hassanean, Hashim A.
A1  - Abdelhameed, Reda F. A.
A1  - Temraz, Tarek A.
A1  - Hajjar, Dina
A1  - Makki, Arwa A.
A1  - Hendawy, Omnia Magdy
A1  - AboulMagd, Asmaa M.
A1  - Youssif, Khayrya A.
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
T1  - Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies
JF  - Molecules
N2  - Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography–mass spectrometry (GC–MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC\(_{50}\) of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2–p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents.
KW  - Holothuria spinifera
KW  - HRMS
KW  - cerebrosides
KW  - molecular docking
KW  - cytotoxicity
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234058
SN  - 1420-3049
VL  - 26
IS  - 6
ER  -