TY - JOUR A1 - Dashti, Yousef A1 - Grkovic, Tanja A1 - Abdelmohsen, Usama Ramadan A1 - Hentschel, Ute A1 - Quinn, Ronald J. T1 - Production of Induced Secondary Metabolites by a Co-Culture of Sponge-Associated Actinomycetes, Actinokineospora sp EG49 and Nocardiopsis sp RV163 JF - MARINE DRUGS N2 - Two sponge-derived actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163, were grown in co-culture and the presence of induced metabolites monitored by H-1 NMR. Ten known compounds, including angucycline, diketopiperazine and beta-carboline derivatives 1-10, were isolated from the EtOAc extracts of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163. Co-cultivation of Actinokineospora sp. EG49 and Nocardiopsis sp. RV163 induced the biosynthesis of three natural products that were not detected in the single culture of either microorganism, namely N-(2-hydroxyphenyl)-acetamide (11), 1,6-dihydroxyphenazine (12) and 5a, 6,11a, 12-tetrahydro-5a, 11a-dimethyl[1,4]benzoxazino[3,2-b][1,4]benzoxazine (13a). When tested for biological activity against a range of bacteria and parasites, only the phenazine 12 was active against Bacillus sp. P25, Trypanosoma brucei and interestingly, against Actinokineospora sp. EG49. These findings highlight the co-cultivation approach as an effective strategy to access the bioactive secondary metabolites hidden in the genomes of marine actinomycetes. KW - co-cultivation KW - induced metabolites KW - sponge-associated actinomyetes KW - NMR fingerprint KW - bioactivity KW - natural products KW - A-D KW - aspergillus fumigatus KW - marine KW - biosynthesis Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116547 SN - 1660-3397 VL - 12 IS - 5 ER - TY - THES A1 - Glaser, Jan T1 - Antileishmanial compounds from Nature - Elucidation of the active principles of an extract from Valeriana wallichii rhizomes T1 - Antileishmaniale Wirkstoffe aus der Natur - Aufklärung des Wirkprinzips eines Wurzelextraktes von Valeriana wallichii N2 - This study is dealing with the bioactivity-guided fractionation of a chloroform extract from pulverized rhizomes of Valeriana wallichii with focus on isolation and structure elucidation of the antileishmanial active principles. N2 - Die vorliegende Studie beschäftigt sich mit der bioaktivitätsgeleiteten Fraktionierung eines Chloroformextraktes aus pulverisierten Rhizomen von Valeriana wallichii mit Schwerpunkt auf der Isolierung und Strukturaufklärung des antileishmanialen Wirkprinzips. KW - Leishmaniose KW - Valeriana wallichii KW - Extrakt KW - Rhizom KW - Naturstoff KW - natural products KW - antileishmanial KW - Valeriana wallichii Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129140 ER - TY - JOUR A1 - Hofmann, Julian A1 - Ginex, Tiziana A1 - Espargaró, Alba A1 - Scheiner, Matthias A1 - Gunesch, Sandra A1 - Aragó, Marc A1 - Stigloher, Christian A1 - Sabaté, Raimon A1 - Luque, F. Javier A1 - Decker, Michael T1 - Azobioisosteres of Curcumin with Pronounced Activity against Amyloid Aggregation, Intracellular Oxidative Stress, and Neuroinflammation JF - Chemistry – A European Journal N2 - Many (poly‐)phenolic natural products, for example, curcumin and taxifolin, have been studied for their activity against specific hallmarks of neurodegeneration, such as amyloid‐β 42 (Aβ42) aggregation and neuroinflammation. Due to their drawbacks, arising from poor pharmacokinetics, rapid metabolism, and even instability in aqueous medium, the biological activity of azobenzene compounds carrying a pharmacophoric catechol group, which have been designed as bioisoteres of curcumin has been examined. Molecular simulations reveal the ability of these compounds to form a hydrophobic cluster with Aβ42, which adopts different folds, affecting the propensity to populate fibril‐like conformations. Furthermore, the curcumin bioisosteres exceeded the parent compound in activity against Aβ42 aggregation inhibition, glutamate‐induced intracellular oxidative stress in HT22 cells, and neuroinflammation in microglial BV‐2 cells. The most active compound prevented apoptosis of HT22 cells at a concentration of 2.5 μm (83 % cell survival), whereas curcumin only showed very low protection at 10 μm (21 % cell survival). KW - amyloid beta KW - bioisosterism KW - natural products KW - neuroprotectivity KW - replica-exchange molecular dynamics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238988 VL - 27 IS - 19 SP - 6015 EP - 6027 ER - TY - THES A1 - Rummey, Christian T1 - 3D-QSAR-Untersuchungen an antimalaria-aktiven Naphthylisochinolin-Alkaloiden T1 - 3D-QSAR-Investigations on antimalarially active Naphthylisoquinoline Alkaloids N2 - Aufbauend auf einen Datensatz von etwa 70 antimalaria-aktiven Verbindungen wurde mit Hilfe des CoMSIA-Verfahrens ein QSAR(Qantitative Structure Activity Relationship)-Modell erstellt, das in der Lage ist antiplasmodiale Aktivitäten von Verbindungen aus der Substanzklasse der Naphthylisochinolin-Alkaloide vorherzusagen. Da die behandelten Strukturen ein sehr kompliziertes konformatives Verhalten aufweisen, mussten für ein möglichst flexibles Alignment (unter Verwendung von FLEXS und GASP) eigene Abläufe entwickelt werden, die schließlich weitestgehend automatisiert werden konnten. Das erstellte Modell erlaubte es darüber hinaus, die für die Aktivität verantwortlichen strukturellen Merkmale zu identifizieren und so entscheidende Anregungen zur Vereinfachung des relativ komplizierten Grundgerüsts zu geben. Die Vorschläge wurden zu einem großen Teil bereits synthetisch verwirklicht, wobei die anschließend experimentell gefundenen Aktivitäten die vorher berechneten sehr gut bestätigten. Die neu entwickelten Substanzen befinden sich derzeit im Patentprüfungsverfahren. N2 - Based on a dataset of about 70 antimalarially-active compounds a QSAR (Qantitative Structure Activity Relationship) model to predict antiplasmodial activities of aphthylisoquinoline alkaloids was developed, using the popular CoMSIA procedure. Since the structures under interest show a quite complicated conformational behaviour, the application of flexible alignment approaches (using FLEXS and GASP) hat to be developed and could be automated to the greatest possible extend. Additionally the QSAR made it possible to identify the structural features responsible for biological activity and decisive clues to simplify some of the quite complicated structural features of the substance class could be given. Some of the proposals made could already be synthetically realized and the experimental activities found confirmed the calculated ones quite satisfactorily. KW - Malaria KW - Naphthylisochinolinalkaloide KW - QSAR KW - Malaria KW - Naturstoffe KW - QSAR KW - Alignment KW - FLEXS KW - malaria KW - natural products KW - QSAR KW - alignment KW - FLEXS Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-4599 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 - Sawatzky, Edgar A1 - Drakopoulos, Antonios A1 - Rölz, Martin A1 - Sotriffer, Christoph A1 - Engels, Bernd A1 - Decker, Michael T1 - Experimental and theoretical investigations into the stability of cyclic aminals JF - Beilstein Journal of Organic Chemistry N2 - Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom. Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account. KW - quantum mechanics KW - hydrolysis KW - kinetics KW - molecular mechanics KW - natural products Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160976 VL - 12 ER -