Tendo como base o escasso conhecimento dos efeitos causados por eucaliptos sobre a biota aquática e o intenso plantio em áreas de entorno de inúmeros lagos no Vale do rio Doce, o presente estudo avaliou a extração, identificação e os efeitos tóxicos dos compostos naturais presentes nas folhas de Eucalyptus grandis e E. urophylla das áreas de entorno das lagoas Palmeirinha e Ferruginha, respectivamente, através de destilação por arraste a vapor de água, cromatografia gasosa de alta resolução (CGC), análise por infravermelho e testes ecotoxicológicos com as águas de decomposição das folhas (laboratório), com os óleos essenciais, extratos hidroalcólicos e aquosos das folhas da serapilheira, 30 e 60 dias após contato com as lagoas. Nos testes de toxicidade foram utilizados organismos zooplanctônicos (Daphnia similis, Daphnia laevis e Ceriodaphnia silvestrii) e bentônicos (Chironomus xanthus). As folhas de E. grandis apresentaram maior rendimento de óleo essencial que as de E. urophylla, tendo sido identificado maior número de substâncias nas folhas de E. urophylla. No caso dos extratos o E. grandis apresentou maior rendimento dos extratos hexânicos, tanto na primeira como na segunda etapa de extração enquanto o E. urophylla apresentou maior rendimento de extrato etanólico. Verificou-se como principais compostos nos extratos de E. urophylla esteróides e triterpenos. Os resultados dos testes de toxicidade aguda realizados com a água de decomposição das duas espécies de eucaliptos mostraram efeito tóxico a Daphnia similis, D. laevis e C.silvestrii e Chironomus xanthus o qual, entretanto, diminuiu com o aumento do tempo de decomposição. Os óleos essenciais apresentaram efeito tóxico em todos os testes realizados com cladóceros (folhas da serapilheira, 30 e 60 dias), assim como os extratos hidroalcoólicos (menos polares) a Chironomus xanthus e aquosos (mais polares) à D. similis e D. laevis verificou-se, portanto, no presente estudo, que os compostos naturais presentes nas folhas de E. grandis e E. urophylla podem afetar a biota aquática, sendo importante o monitoramento de ambientes aquáticos circundados por monoculturas de Eucalyptus spp. / Based on the scarce knowledge of the effect caused by eucalyptus on aquatic biota and the intense plantation in the surroundings of innumerable lakes in the Valley of Rio Doce, the present study evaluated extraction, identification and toxic effect of natural compounds found in leaves of Eucalyptus grandis and E. urophylla nearby Palmeirinha and Ferruginha lagoons, respectively, through vapor dragging distillation, high resolution gas chromatography (HRGC), Infrared spectroscopy (IR) and ecotoxicological tests with leaves decomposition water (laboratory), essential oils, hydroalcoholic and aqueous extracts of litter leaves, and after 30 and 60 days in contact with the lagoons. For the toxicity tests, zooplanktonic (Daphnia similis, Daphnia laevis and Ceriodaphnia silvestrii) and benthic (Chironomus xanthus) organisms were used. The leaves of E. grandis showed higher outcome of essential oils compared to E. urophylla, being identified a higher number of substances in E. urophylla leaves. In the case of extracts, E. grandis showed higher outcome of hexanic extracts in the first and second steps of extractions, while E. urophylla presented higher outcome of ethanolic extracts. The main compounds found in E. urophylla extracts were steroids and triterpenes, and in E. grandis were saponins, steroids and triterpenes. The results of the acute ecotoxicological tests carried out with decomposition water of both eucalyptus species showed toxic effect to Daphnia similis, D. laevis, C. silvestrii and Chironomus xanthus, which, however, decreased with decomposition time. The essential oils, showed toxic effect in all tests performed with cladocerans (litter leaves, 30 and 60 days), as well as the hydroalcoholic extracts to Chironomus xanthus and aqueous to D. similis and D. laevis. Thus, it was verified, in the present study, that the natural compounds found in E. grandis and E urophylla leaves can affect the aquatic biota, being important the monitoring of aquatic environments surrounded by Eucalyptus monocultures.

Die Ziele dieser Arbeit waren die Darstellung der Naturstoffe Murrayachinon-B–E und Pyrayachinon-A–C, sowie die Synthese einiger nicht natürlicher, potentiell anti-Tuberkulose-aktiver Carbazole und Carbazolchinone. Für die Darstellung der aus der Pflanze Murraya euchrestifolia Hayata isolierten Naturstoffe wurden verschiedene synthetische Herangehensweisen untersucht: Die Transformation eines 7 Hydroxycarbazolchinons in die Zielverbindungen gelang nicht, ebenso wie die Syntheseroute über eine trioxygenierte Vorstufe. 7-Methoxy-3-methyl-1-tosyloxycarbazol (A) ließ sich jedoch in einer Ausbeute von 76 % über drei Stufen darstellen. Ausgehend von A konnten die Zielverbindungen regioselektiv in fünf bis sieben Stufen in Gesamtausbeuten von 10 % bis 46 % synthetisiert werden. Der Pyranring in Pyrayachinon-A wurde dabei über eine Sequenz aus Bromierung, Prenylierung, Cyclisierung und Oxidation aufgebaut. Die Anellierung der Pyranringe in Pyrayachinon-B und –C erfolgte, nach Methyletherspaltung an A in zwei Stufen. Die Einführung der Prenyl- und Geranylgruppen für die Synthese der Murrayachinone gelang durch reduktive Pyranringöffnung bzw. über eine Sequenz aus Methyletherspaltung, Propargylierung, partieller Hydrierung und Umlagerung. Außerdem wurde für Murrayafolin-B, Bismurrayafolin-B und -D über diese Syntheseroute ein Zugang geschaffen. Diese Verbindungen konnten, ausgehend von A, in sechs bzw. sieben Stufen in Gesamtausbeuten von 39 % bis 53 % dargestellt werden. Im Vergleich zu den bislang beschriebenen Synthesen dieser Verbindungen konnten alle Gesamtausbeuten signifikant gesteigert werden. Besonders hervorzuheben sind die Synthesen von Murrayafolin-B (bislang: 0.4 %, in dieser Arbeit: 40.0 %) und Pyrayachinon-A (bislang: 3.0 %, in dieser Arbeit: 22.1 %). Überdies wurde erstmalig die palladiumkatalysierte oxidative Cyclisierung eines O-tosylgeschützten Diarylamins zu einem Carbazol beschrieben. In Fortführung vorangegangener Arbeiten wurden zehn bislang nicht beschriebene Derivate des anti-Tuberkulose-aktiven 3-Methoxy-2-methylcarbazol-1,4-chinons dargestellt, darunter neun Carbazolchinone und ein Carbazol. Die Synthese der Carbazolchinone gelang palladiumkatalysiert in je vier bis sechs Stufen. Das Carbazol wurde eisenvermittelt über fünf Stufen dargestellt. Die Untersuchung der Aktivität gegenüber Mycobacterium tuberculosis steht noch aus.

This master thesis is aimed at the issue of activating methods of teaching, namely didactic games in Chemistry lessons. In the theoretical part activating methods of teaching, didactic games, visualization of molecules and the programming language Java were described. The aim of the practical part was to create the "Chemical 3D Matching Pairs Game", dealing with two topics - the naming of organic compounds and the natural products. The 3D structure of used compounds can be examined by students during playing the game. The created game was tested by secondary school students and its didactic potential was evaluated. The main benefits of the game were student activation and a high motivational character.

<p>With 2.1 million new cases, breast cancer is the most common cancer in women. Triple negative breast cancer (TNBC), which is 15-20% of these breast cancer cases is clinically negative for expression of estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2) receptors<a>.</a> It is characterized by its unique molecular profile, aggressive behavior, distinct patterns of metastasis, and lack of targeted therapies. TNBCs utilize glycolysis for growth, proliferation, invasiveness, chemotherapeutic resistance and hence has poor therapeutic response. There is an urgent need for novel/alternate therapeutic strategies beyond current standard of treatment for this subset of high-risk patients. Electrical pulse-based chemotherapy, known as electrochemotherapy (ECT) could be a viable option for TNBC therapy. ECT involves the local application of precisely controlled electrical pulses to reversibly permeabilize the cell membrane for enhanced uptake. ECT can increase the cytotoxicity of the chemotherapeutics up-to 1000 times, facilitating a potent local cytotoxic effect. </p> <p>The high cost and severe side-effects of conventional chemotherapeutics motivate the application of effective natural compounds. Combining electrical pulses with natural compounds will enhance the treatment efficacy. This dissertation focuses on curcumin, the yellow pigment of natural herb turmeric, that has been used for over 5000 years for its excellent anticancer properties. Previous studies have demonstrated the effectiveness of curcumin for treating multiple cancers, including TNBC, with limited side effects. The potency of curcumin can be enhanced further by combining it with ECT to provide an attractive and cost-effective alternative for TNBC treatment. </p> <p>Towards this we studied the effect of ECT with curcumin on MDA-MB-231 cell line, a human adenocarcinoma epithelial TNBC cell line. We performed various assays, including cell viability, colony forming, cell cycle, apoptosis, H₂O₂ reactive oxygen species (ROS), immunoblotting, real time quantitative PCR (qPCR), and cellular metabolites detection to study the impact of ECT with curcumin on MDA-MB-231 cells. In addition, to better understand the underlying mechanisms, we used high throughput, label-free quantitative proteomics. While several studies have attempted to define the mechanism of action of curcumin on cancer cells, little is known on the action mechanism of the curcumin delivered with electrical pulses. This work unravels the molecular mechanism behind the enhanced effects observed under the ECT-based curcumin therapy in TNBC cells, employing a high-throughput, quantitative, label-free mass spectroscopy-based proteomics approach. The proteomics approach provides information on the thousands of cellular proteins involved in the cellular process, allowing a comprehensive understanding of the electro-curcumin-therapy mechanism. Similar studies were also performed for ECT with cisplatin to compare the efficacy of the electro-curcumin-therapy to the standard stand-alone cisplatin-based therapy.</p> <p>Our results revealed a switch in the metabolism from glycolysis to mitochondrial metabolic pathways. This metabolic switch caused an excessive production of H₂O₂ ROS to inflict apoptotic cell death in MDA-MB-231 cells, demonstrating the potency of this ECT based curcumin therapy. These results encourage further studies to extend the application of ECT for clinical practice.</p>