{"id":{"repo_id":"bayreuth","oai_identifier":"oai:epub.uni-bayreuth.de:1671"},"canonical_url":"https://search.dev.ndltd.org/etd/bayreuth/oai:epub.uni-bayreuth.de:1671","repository":{"repo_id":"bayreuth","name":"Universität Bayreuth","base_url":"https://epub.uni-bayreuth.de/cgi/oai2"},"display":{"title":"Biochemical studies of targeted and bimodal analogues of the natural anticancer compounds combretastatin A-4 and illudin M","abstract":"This thesis presents a study on novel chemotherapeutics based on naturally designed scaffolds. The cytotoxicity of promising pharmaceutical compounds was tested on various cells of neural and/or cancerous origin, monitoring their specificity, re-growth retardation and mechanism of apoptosis induction. The proposed drug uptake was analysed using specific inhibitors to disable certain transporters/carriers. Changes in the shapes of cellular and sub-cellular components resulting from drug treatment were observed by light microscopy, immune-fluorescence microscopy, time-lapse recording microscopy and transmission electron microscopy. The apoptotic signals, increased cellular activity of caspase-3 or redundant calcium level, were monitored during drug incubation. Because DNA-degradation plays an important role in apoptosis, DNA-drug interactions affecting chromosomal or plasmid DNA were investigated from various perspectives. Since resistance is a constricting factor for drug efficiency, the interaction of the drugs with glutathione and various efflux transporters were analysed.","abstract_html":"This thesis presents a study on novel chemotherapeutics based on naturally designed scaffolds. The cytotoxicity of promising pharmaceutical compounds was tested on various cells of neural and/or cancerous origin, monitoring their specificity, re-growth retardation and mechanism of apoptosis induction. The proposed drug uptake was analysed using specific inhibitors to disable certain transporters/carriers. Changes in the shapes of cellular and sub-cellular components resulting from drug treatment were observed by light microscopy, immune-fluorescence microscopy, time-lapse recording microscopy and transmission electron microscopy. The apoptotic signals, increased cellular activity of caspase-3 or redundant calcium level, were monitored during drug incubation. Because DNA-degradation plays an important role in apoptosis, DNA-drug interactions affecting chromosomal or plasmid DNA were investigated from various perspectives. Since resistance is a constricting factor for drug efficiency, the interaction of the drugs with glutathione and various efflux transporters were analysed.","abstract_has_math":false,"creators":["Zoldakova, Miroslava"],"institution":"Universität Bayreuth","degree_name":null,"degree_level":"thesis.doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Schobert, Rainer"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-07-04","date_published":"2011-07-04","updated_at":"2026-07-27T18:49:36Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://epub.uni-bayreuth.de/id/eprint/1671/","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Schobert, Rainer"]},{"key":"dc:creator","label":"Author","values":["Zoldakova, Miroslava"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Universität Bayreuth"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["thesis.doctoral"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Universität Bayreuth"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This thesis presents a study on novel chemotherapeutics based on naturally designed scaffolds. The cytotoxicity of promising pharmaceutical compounds was tested on various cells of neural and/or cancerous origin, monitoring their specificity, re-growth retardation and mechanism of apoptosis induction. The proposed drug uptake was analysed using specific inhibitors to disable certain transporters/carriers. Changes in the shapes of cellular and sub-cellular components resulting from drug treatment were observed by light microscopy, immune-fluorescence microscopy, time-lapse recording microscopy and transmission electron microscopy. The apoptotic signals, increased cellular activity of caspase-3 or redundant calcium level, were monitored during drug incubation. Because DNA-degradation plays an important role in apoptosis, DNA-drug interactions affecting chromosomal or plasmid DNA were investigated from various perspectives. Since resistance is a constricting factor for drug efficiency, the interaction of the drugs with glutathione and various efflux transporters were analysed.","Diese Arbeit stellt eine Studie über neue Chemotherapeutika dar, welche ausgehend von Naturstoff-basierenden Strukturen dargestellt worden sind. Die cytotoxische Wirkung der vielversprechendsten Verbindungen wurde an verschiedenen Zellen neuralen und/oder malignen Ursprungs getestet, und ihre Spezifität, Wachstumshemmung sowie Mechanismen der Apoptoseinduktion wurden analysiert. Mutmaßliche Wege der Wirkstoffaufnahme wurden durch Einsatz spezifischer Hemmer bestimmter Transport- und Carrierproteine untersucht. Wirkstoff-induzierte morphologische Veränderungen zellulärer und sub-zellulärer Strukturen wurden Licht-mikroskopisch, Immunfluoreszenz-mikroskopisch, Zeitraffer-mikroskopisch und Transmissionselektronen-mikroskopisch beobachtet. Durch einzelne Wirkstoffe hervorgerufene apoptotische Signale wie verstärkte Caspase-3-Aktivität oder erhöhter Calciumspiegel wurden analysiert. Da die DNASchädigung und der DNA-Abbau eine wichtige Rolle zur Apoptoseeinleitung und auch während der Apoptose spielt, wurden DNA-Wirkstoff-Wechselwirkungen bezüglich chromosomaler und Plasmid-DNA von verschiedenen Blickwinkeln aus untersucht. Schließlich stellt die Wirkstoffresistenz von Tumorzellen einen limitierenden Faktor dar, welche in entsprechenden Experimenten zur Interaktion der Wirkstoffe mit Glutathion oder mit verschiedenen Efflux-Transportern analysiert wurde."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Biochemical studies of targeted and bimodal analogues of the natural anticancer compounds combretastatin A-4 and illudin M"]}]}],"canonical_facts":{"dc:contributor":["Schobert, Rainer"],"dc:creator":["Zoldakova, Miroslava"],"dc:description.abstract":["This thesis presents a study on novel chemotherapeutics based on naturally designed scaffolds. The cytotoxicity of promising pharmaceutical compounds was tested on various cells of neural and/or cancerous origin, monitoring their specificity, re-growth retardation and mechanism of apoptosis induction. The proposed drug uptake was analysed using specific inhibitors to disable certain transporters/carriers. Changes in the shapes of cellular and sub-cellular components resulting from drug treatment were observed by light microscopy, immune-fluorescence microscopy, time-lapse recording microscopy and transmission electron microscopy. The apoptotic signals, increased cellular activity of caspase-3 or redundant calcium level, were monitored during drug incubation. Because DNA-degradation plays an important role in apoptosis, DNA-drug interactions affecting chromosomal or plasmid DNA were investigated from various perspectives. Since resistance is a constricting factor for drug efficiency, the interaction of the drugs with glutathione and various efflux transporters were analysed.","Diese Arbeit stellt eine Studie über neue Chemotherapeutika dar, welche ausgehend von Naturstoff-basierenden Strukturen dargestellt worden sind. Die cytotoxische Wirkung der vielversprechendsten Verbindungen wurde an verschiedenen Zellen neuralen und/oder malignen Ursprungs getestet, und ihre Spezifität, Wachstumshemmung sowie Mechanismen der Apoptoseinduktion wurden analysiert. Mutmaßliche Wege der Wirkstoffaufnahme wurden durch Einsatz spezifischer Hemmer bestimmter Transport- und Carrierproteine untersucht. Wirkstoff-induzierte morphologische Veränderungen zellulärer und sub-zellulärer Strukturen wurden Licht-mikroskopisch, Immunfluoreszenz-mikroskopisch, Zeitraffer-mikroskopisch und Transmissionselektronen-mikroskopisch beobachtet. Durch einzelne Wirkstoffe hervorgerufene apoptotische Signale wie verstärkte Caspase-3-Aktivität oder erhöhter Calciumspiegel wurden analysiert. Da die DNASchädigung und der DNA-Abbau eine wichtige Rolle zur Apoptoseeinleitung und auch während der Apoptose spielt, wurden DNA-Wirkstoff-Wechselwirkungen bezüglich chromosomaler und Plasmid-DNA von verschiedenen Blickwinkeln aus untersucht. Schließlich stellt die Wirkstoffresistenz von Tumorzellen einen limitierenden Faktor dar, welche in entsprechenden Experimenten zur Interaktion der Wirkstoffe mit Glutathion oder mit verschiedenen Efflux-Transportern analysiert wurde."],"dc:format.medium":["application/pdf"],"dc:publisher":["Universität Bayreuth"],"dc:title":["Biochemical studies of targeted and bimodal analogues of the natural anticancer compounds combretastatin A-4 and illudin M"],"dc:type":["doctoralThesis"],"thesis:degree_level":["thesis.doctoral"],"thesis:institution_name":["Universität Bayreuth"]},"updated_at":"2026-07-27T18:49:36Z"}