TY - JOUR A1 - Fayez, Shaimaa A1 - Feineis, Doris A1 - Aké Assi, Laurent A1 - Seo, Ean-Jeong A1 - Efferth, Thomas A1 - Bringmann, Gerhard T1 - Ancistrobreveines A–D and related dehydrogenated naphthylisoquinoline alkaloids with antiproliferative activities against leukemia cells, from the West African liana Ancistrocladus abbreviatus JF - RSC Advances N2 - A unique series of six biaryl natural products displaying four different coupling types (5,10 , 7,10 , 7,80 , and 5,80) were isolated from the roots of the West African liana Ancistrocladus abbreviatus (Ancistrocladaceae). Although at first sight structurally diverse, these secondary metabolites all have in common that they belong to the rare group of naphthylisoquinoline alkaloids with a fully dehydrogenated isoquinoline portion. Among the African Ancistrocladus species, A. abbreviatus is so far only the second one that was found to produce compounds with such a molecular entity. Here, we report on four new representatives, named ancistrobreveines A–D (12–14, and 6). They were identified along with the two known alkaloids 6-O-methylhamateine (4) and entdioncophylleine A (10). The two latter naphthylisoquinolines had so far only been detected in Ancistrocladus species from Southeast Asia. All of these fully dehydrogenated alkaloids have in common being optically active despite the absence of stereogenic centers, due to the presence of the rotationally hindered biaryl axis as the only element of chirality. Except for ent-dioncophylleine A (10), which lacks an oxygen function at C-6, the ancistrobreveines A–D (12–14, and 6) and 6-O-methylhamateine (4) are 6-oxygenated alkaloids, and are, thus, typical ‘Ancistrocladaceae-type’ compounds. Ancistrobreveine C (14), is the first – and so far only – example of a 7,80-linked fully dehydrogenated naphthylisoquinoline discovered in nature that is configurationally stable at the biaryl axis. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR) and chiroptical (electronic circular dichroism) methods. Ancistrobreveine C (14) and 6-O-methylhamateine (4) exhibited strong antiproliferative activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrugresistant subline, CEM/ADR5000. KW - chemistry Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201686 VL - 9 IS - 28 ER - TY - JOUR A1 - Mufusama, Jean-Pierre A1 - Feineis, Doris A1 - Mudogo, Virima A1 - Kaiser, Marcel A1 - Brun, Reto A1 - Bringmann, Gerhard T1 - Antiprotozoal dimeric naphthylisoquinolines, mbandakamines B\(_3\) and B\(_4\), and related 5,8′-coupled monomeric alkaloids, ikelacongolines A–D, from a Congolese Ancistrocladus liana JF - RSC Advances N2 - From the leaves of a botanically and phytochemically as yet unexplored Ancistrocladus liana discovered in the rainforests of the Central region of the Democratic Republic of the Congo in the vicinity of the town of Ikela, six new naphthylisoquinoline alkaloids were isolated, viz., two constitutionally unsymmetric dimers, the mbandakamines B\(_3\) (3) and B\(_4\) (4), and four related 5,8′-linked monomeric alkaloids, named ikelacongolines A–D (5a, 5b, 6, and 7). The dimers 3 and 4 are structurally unusual quateraryls comprising two 5,8′-coupled monomers linked via a sterically strongly constrained 6′,1′′-connection between their naphthalene units. These compounds contain seven elements of chirality, four stereogenic centers and three consecutive chiral axes. They were identified along with two known related compounds, the mbandakamines A (1) and B\(_2\) (2), which had so far only been detected in two Ancistrocladus species indigenous to the Northwestern Congo Basin. In addition, five known monomeric alkaloids, previously found in related Central African Ancistrocladus species, were isolated from the here investigated Congolese liana, three of them belonging to the subclass of 5,8′-coupled naphthylisoquinoline alkaloids, whereas two compounds exhibited a less frequently occurring 7,8′-biaryl linkage. The stereostructures of the new alkaloids were established by spectroscopic (in particular HRESIMS, 1D and 2D NMR), chemical (oxidative degradation), and chiroptical (electronic circular dichroism) methods. The mbandakamines B\(_3\) (3) and B\(_4\) (4) displayed pronounced activities in vitro against the malaria parasite Plasmodium falciparum and the pathogen of African sleeping sickness, Trypanosoma brucei rhodesiense. KW - chemistry Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201141 VL - 9 IS - 21 ER - TY - JOUR A1 - Pimentel-Elardo, Sheila M. A1 - Buback, Verena A1 - Gulder, Tobias A. M. A1 - Bugni, Tim S. A1 - Reppart, Jason A1 - Bringmann, Gerhard A1 - Ireland, Chris M. A1 - Schirmeister, Tanja A1 - Hentschel, Ute T1 - New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities JF - Marine drugs N2 - Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range. KW - cysteine protease KW - drugs KW - streptomyces KW - discovery KW - anti-trypanosomal KW - protease inhibition KW - Streptomyces axinellae KW - marine sponge KW - tetromycin Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141171 VL - 9 IS - 10 ER - TY - JOUR A1 - Fayez, Shaimaa A1 - Feineis, Doris A1 - Mudogo, Virima A1 - Awale, Suresh A1 - Bringmann, Gerhard T1 - Ancistrolikokines E-H and related 5,8\('\)-coupled naphthylisoquinoline alkaloids from the Congolese liana \(Ancistrocladus\) \(likoko\) with antiausterity activities against PANC-1 human pancreatic cancer cells JF - RSC Advances N2 - A striking feature of the metabolite profile of \(Ancistrocladus\) \(likoko\) (Ancistrocladaceae) is the exclusive production of 5,8\('\)-linked naphthylisoquinoline alkaloids varying in their OMe/OH substitution patterns and in the hydrogenation degree in their isoquinoline portions. Here we present nine new compounds of this coupling type isolated from the twigs of this remarkable Central African liana. Three of them, the ancistrolikokines E (9), E\(_2\) (10), and F (11), are the first 5,8\('\)-linked naphthyldihydroisoquinolines found in nature with \(R\)-configuration at C-3. The fourth new metabolite, ancistrolikokine G (12), is so far the only representative of the 5,8\('\)-coupling type that belongs to the very rare group of alkaloids with a fully dehydrogenated isoquinoline portion. Moreover, five new \(N\)-methylated naphthyltetrahydroisoquinolines, named ancistrolikokines A\(_2\) (13), A\(_3\) (14), C\(_2\) (5), H (15), and H\(_2\) (16) are presented, along with six known 5,8\('\)-linked alkaloids, previously identified in related African \(Ancistrocladus\) species, now found for the first time in \(A.\) \(likoko\). The structural elucidation was achieved by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and by chemical (oxidative degradation) and chiroptical (electronic circular dichroism) methods. The new ancistrolikokines showed moderate to good preferential cytotoxic activities towards pancreatic PANC-1 cells in nutrient-deprived medium (NDM), without causing toxicity under normal, nutrient-rich conditions, with ancistrolikokine H\(_2\) (16) being the most potent compound. KW - chemistry KW - Ancistrocladus likoko KW - alkaloids KW - bioactive compound KW - anti-cancer-agent KW - pancreatic cancer KW - naphthylisoquinoline alkaloid KW - spectroscopic analysis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172008 VL - 7 IS - 85 ER - TY - JOUR A1 - Pimentel-Elardo, Sheila M. A1 - Buback, Verena A1 - Gulder, Tobias A. M. A1 - Bugni, Tim S. A1 - Reppart, Jason A1 - Bringmann, Gerhard A1 - Ireland, Chris M. A1 - Schirmeister, Tanja A1 - Hentschel, Ute T1 - New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities N2 - Four new tetromycin derivatives, tetromycins 1–4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001T cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV Mpro, and PLpro. The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with Ki values in the low micromolar range. KW - Biologie KW - tetromycin KW - anti-trypanosomal KW - protease inhibition KW - Streptomyces axinellae KW - marine sponge Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75465 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 - 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 - Wang, Hui A1 - Li, Min-Yi A1 - Katele, Félix Zongwe A1 - Satyanandamurty, Tirumani A1 - Wu, Jun A1 - Bringmann, Gerhard T1 - Decandrinin, an unprecedented \(C_9\)-spiro-fused 7,8-\( seco-ent\)-abietane from the Godavari mangrove \(Ceriops\ decandra\) JF - Beilstein Journal of Organic Chemistry N2 - Decandrinin (1), an unprecedented \(C_9\)-spiro-fused 7,8-\(seco-ent\)-abietane, was obtained from the bark of an Indian mangrove, \(Ceriops\ decandra\), collected in the estuary of Godavari, Andhra Pradesh. The constitution and the relative configuration of 1 were determined by HRMS (ESI) and extensive NMR investigations, and the absolute configuration by circular dichroism (CD) and optical-rotatory dispersion (ORD) spectroscopy in combination with quantum-chemical calculations. Decandrinin is the first 7,8-\(seco-ent\)-abietane. KW - ceriops decandra KW - abietane KW - absolute configuration KW - circular dichroism KW - decandrinin KW - rhizophoraceae Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119983 SN - 1860-5397 VL - 10 ER - TY - JOUR A1 - Messi, Bernadette Biloa A1 - Ndjoko-Ioset, Karine A1 - Hertlein-Amslinger, Barbara A1 - Lannang, Alain Meli A1 - Nkengfack, Augustin E. A1 - Wolfender, Jean-Luc A1 - Hostettmann, Kurt A1 - Bringmann, Gerhard T1 - Preussianone, a New Flavanone-Chromone Biflavonoid from Garcinia preussii Engl. JF - Molecules N2 - A new flavanone-chromone biflavonoid, preussianone (1), has been isolated from the leaves of Garcinia preussii, along with four known biflavonoids. The absolute stereostructures were elucidated by chemical, spectroscopic, and chiroptical methods. The biological properties of the new biflavonoid against several bacterial strains were evaluated. KW - multiflora KW - minimal inhibitory concentration KW - absolute configuration KW - circular dichroism KW - C-13 NMR KW - guttiferae KW - flavenoids KW - extractives KW - biflavanoids KW - livingstonei KW - high-temperature NMR KW - antibacterial activity KW - Garcinia biflavonoids Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130881 VL - 17 IS - 5 ER - TY - JOUR A1 - Jansen, Nils A1 - Ohlendorf, Birgit A1 - Erhard, Arlette A1 - Bruhn, Torsten A1 - Bringmann, Gerhard A1 - Imhoff, Johannes F. T1 - Helicusin E, Isochromophilone X and Isochromophilone XI: New Chloroazaphilones Produced by the Fungus Bartalinia robillardoides Strain LF550 JF - Marine Drugs N2 - Microbial studies of the Mediterranean sponge Tethya aurantium led to the isolation of the fungus Bartalinia robillardoides strain LF550. The strain produced a number of secondary metabolites belonging to the chloroazaphilones. This is the first report on the isolation of chloroazaphilones of a fungal strain belonging to the genus Bartalinia. Besides some known compounds (helicusin A (1) and deacetylsclerotiorin (2)), three new chloroazaphilones (helicusin E (3); isochromophilone X (4) and isochromophilone XI (5)) and one new pentaketide (bartanolide (6)) were isolated. The structure elucidations were based on spectroscopic analyses. All isolated compounds revealed different biological activity spectra against a test panel of four bacteria: three fungi; two tumor cell lines and two enzymes. KW - tethya aurantium KW - marine natural product KW - azaphilone KW - pentaketide KW - bartalinia robillardoides Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129649 VL - 11 IS - 3 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 - Kunz, Anna Lena A1 - Labes, Antje A1 - Wiese, Jutta A1 - Bruhn, Torsten A1 - Bringmann, Gerhard A1 - Imhoff, Johannes F. T1 - Nature's Lab for Derivatization: New and Revised Structures of a Variety of Streptophenazines Produced by a Sponge-Derived Streptomyces Strain JF - Marine Drugs N2 - Eight streptophenazines (A-H) have been identified so far as products of Streptomyces strain HB202, which was isolated from the sponge Halichondria panicea from the Baltic Sea. The variation of bioactivities based on small structural changes initiated further studies on new derivatives. Three new streptophenazines (I-K) were identified after fermentation in the present study. In addition, revised molecular structures of streptophenazines C, D, F and H are proposed. Streptophenazines G and K exhibited moderate antibacterial activity against the facultative pathogenic bacterium Staphylococcus epidermidis and against Bacillus subtilis. All tested compounds (streptophenazines G, I-K) also showed moderate activities against PDE 4B. KW - marine natural product KW - phenazine KW - Baltic Sea KW - streptomyces KW - halichondria panicea KW - obstructive pulmonary disease KW - phosphodiesterase-4 inhibitor KW - absolute configuration KW - biosynthesis KW - rofumilast Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116816 SN - 1660-3397 VL - 12 IS - 4 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 - 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 - Fayez, Shaimaa A1 - Bruhn, Torsten A1 - Feineis, Doris A1 - Assi, Laurent Aké A1 - Kushwaha, Prem Prakash A1 - Kumar, Shashank A1 - Bringmann, Gerhard T1 - Naphthylisoindolinone alkaloids: the first ring-contracted naphthylisoquinolines, from the tropical liana Ancistrocladus abbreviatus, with cytotoxic activity JF - RSC Advances N2 - The West African liana Ancistrocladus abbreviatus is a rich source of structurally most diverse naphthylisoquinoline alkaloids. From its roots, a series of four novel representatives, named ancistrobrevolines A–D (14–17) have now been isolated, displaying an unprecedented heterocyclic ring system, where the usual isoquinoline entity is replaced by a ring-contracted isoindolinone part. Their constitutions were elucidated by 1D and 2D NMR and HR-ESI-MS. The absolute configurations at the chiral axis and at the stereogenic center were assigned by using experimental and computational electronic circular dichroism (ECD) investigations and a ruthenium-mediated oxidative degradation, respectively. For the biosynthetic origin of the isoindolinones from ‘normal’ naphthyltetrahydroisoquinolines, a hypothetic pathway is presented. It involves oxidative decarboxylation steps leading to a ring contraction by a benzilic acid rearrangement. Ancistrobrevolines A (14) and B (15) were found to display moderate cytotoxic effects (up to 72%) against MCF-7 breast and A549 lung cancer cells and to reduce the formation of spheroids (mammospheres) in the breast cancer cell line. KW - Naphthylisoindolinone alkaloids Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300766 VL - 12 IS - 45 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 - 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 - Rushdi, Mohammed I. A1 - Abdel-Rahman, Iman A. M. A1 - Attia, Eman Zekry A1 - Saber, Hani A1 - Saber, Abdullah A. A1 - Bringmann, Gerhard A1 - Abdelmohsen, Usama Ramadan T1 - The biodiversity of the genus Dictyota: phytochemical and pharmacological natural products prospectives JF - Molecules N2 - Although a broad variety of classes of bioactive compounds have already been isolated from seaweeds of the genus Dictyota, most different species are still chemically and biologically unexplored. Dictyota species are well-known brown seaweeds belonging to the Dictyotaceae (Phaeophyta). The phytochemical composition within the genus Dictyota has recently received considerable interest, and a vast array of components, including diterpenes, sesquiterepenes, sterols, amino acids, as well as saturated and polyunsaturated fatty acids, have been characterized. The contribution of these valued metabolites to the biological potential, which includes anti-proliferative, anti-microbial, antiviral, antioxidant, anti-inflammatory, and anti-hyperpigmentation activities, of the genus Dictyota has also been explored. Therefore, this is the most comprehensive review, focusing on the published literature relevant to the chemically and pharmacologically diverse biopharmaceuticals isolated from different species of the genus Dictyota during the period from 1976 to now. KW - Phaeophyceae KW - Dictyotaceae KW - marine macroalgae KW - brown seaweeds KW - natural products KW - bioactivities KW - Dictyota Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302428 SN - 1420-3049 VL - 27 IS - 3 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 - Zahran, Eman Maher A1 - Albohy, Amgad A1 - Khalil, Amira A1 - Ibrahim, Alyaa Hatem A1 - Ahmed, Heba Ali A1 - El-Hossary, Ebaa M. A1 - Bringmann, Gerhard A1 - Abdelmohsen, Usama Ramadan T1 - Bioactivity Potential of Marine Natural Products from Scleractinia-Associated Microbes and In Silico Anti-SARS-COV-2 Evaluation JF - Marine Drugs N2 - Marine organisms and their associated microbes are rich in diverse chemical leads. With the development of marine biotechnology, a considerable number of research activities are focused on marine bacteria and fungi-derived bioactive compounds. Marine bacteria and fungi are ranked on the top of the hierarchy of all organisms, as they are responsible for producing a wide range of bioactive secondary metabolites with possible pharmaceutical applications. Thus, they have the potential to provide future drugs against challenging diseases, such as cancer, a range of viral diseases, malaria, and inflammation. This review aims at describing the literature on secondary metabolites that have been obtained from Scleractinian-associated organisms including bacteria, fungi, and zooxanthellae, with full coverage of the period from 1982 to 2020, as well as illustrating their biological activities and structure activity relationship (SAR). Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and 15 compounds were selected. The selected compounds were virtually investigated for potential inhibition for SARS-CoV-2 targets using molecular docking studies. Promising potential results against SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented. KW - Scleractinia KW - marine bacteria KW - marine fungi KW - zooxanthellae KW - marine natural products KW - ADME analysis KW - SARS-CoV-2 KW - molecular docking KW - RNA-dependent RNA polymerase KW - methyltransferase Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220041 SN - 1660-3397 VL - 18 IS - 12 ER - TY - JOUR A1 - Hofmann, Julian A1 - Fayez, Shaimaa A1 - Scheiner, Matthias A1 - Hoffmann, Matthias A1 - Oerter, Sabrina A1 - Appelt‐Menzel, Antje A1 - Maher, Pamela A1 - Maurice, Tangui A1 - Bringmann, Gerhard A1 - Decker, Michael T1 - Sterubin: Enantioresolution and Configurational Stability, Enantiomeric Purity in Nature, and Neuroprotective Activity in Vitro and in Vivo JF - Chemistry – A European Journal N2 - Alzheimer′s disease (AD) is a neurological disorder with still no preventive or curative treatment. Flavonoids are phytochemicals with potential therapeutic value. Previous studies described the flavanone sterubin isolated from the Californian plant Eriodictyon californicum as a potent neuroprotectant in several in vitro assays. Herein, the resolution of synthetic racemic sterubin (1) into its two enantiomers, (R)‐1 and (S)‐1, is described, which has been performed on a chiral chromatographic phase, and their stereochemical assignment online by HPLC‐ECD coupling. (R)‐1 and (S)‐1 showed comparable neuroprotection in vitro with no significant differences. While the pure stereoisomers were configurationally stable in methanol, fast racemization was observed in the presence of culture medium. We also established the occurrence of extracted sterubin as its pure (S)‐enantiomer. Moreover, the activity of sterubin (1) was investigated for the first time in vivo, in an AD mouse model. Sterubin (1) showed a significant positive impact on short‐ and long‐term memory at low dosages. KW - Alzheimer′s disease KW - chiral resolution KW - circular dichroism KW - Eriodictyon californicum KW - flavonoids KW - sterubin Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215993 VL - 26 IS - 32 SP - 7299 EP - 7308 ER - TY - JOUR A1 - Tshitenge Tshitenge, Dieudonné A1 - Bruhn, Torsten A1 - Feineis, Doris A1 - Mudogo, Virima A1 - Kaiser, Marcel A1 - Brun, Reto A1 - Bringmann, Gerhard T1 - An unusually broad series of seven cyclombandakamines, bridged dimeric naphthylisoquinoline alkaloids from the Congolese liana Ancistrocladus ealaensis JF - Scientific Reports N2 - A series of seven unusual dimeric naphthylisoquinoline alkaloids was isolated from the leaves of the tropical liana Ancistrocladus ealaensis J. Léonard, named cyclombandakamine A (1), 1-epi-cyclombandakamine A (2), and cyclombandakamines A3–7 (3–7). These alkaloids have a chemically thrilling structural array consisting of a twisted dihydrofuran-cyclohexenone-isochromene system. The 1′″-epimer of 4, cyclombandakamine A1 (8), had previously been discovered in an unidentified Ancistrocladus species related to A. ealaensis. Both lianas produce the potential parent precursor, mbandakamine A (9), but only A. ealaensis synthesizes the corresponding cyclized form, along with a broad series of slightly modified analogs. The challenging isolation required, besides multi-dimensional chromatography, the use of a pentafluorophenyl stationary phase. Featuring up to six stereocenters and two types of chiral axes, their structures were elucidated by means of 1D and 2D NMR, HRESIMS, in combination with oxidative chemical degradation experiments as well as chiroptical (electronic circular dichroism spectroscopy) and quantum chemical calculations. Compared to the ‘open-chain’ parent compound 9, these dimers displayed rather moderate antiplasmodial activities. KW - Screening KW - Solution-state NMR KW - Stereochemistry KW - Structure elucidation Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200759 VL - 9 ER - TY - JOUR A1 - Tshitenge, Dieudonné Tshitenge A1 - Feineis, Doris A1 - Mudogo, Virima A1 - Kaiser, Marcel A1 - Brun, Reto A1 - Bringmann, Gerhard T1 - Antiplasmodial Ealapasamines A-C,'Mixed' Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis JF - Scientific Reports N2 - Three unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1–3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. Léonard. These ‘mixed’, constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1–3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range. KW - structure elucidation KW - stereochemistry KW - Ancistrocladus ealaensis KW - dimers Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170645 VL - 7 IS - 5767 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 -