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1	Synthese von Tetragastrin-CC-1065-Konjugaten und verwandten Verbindungen für eine selektive Krebstherapie / Synthesis of Tetragastrin-CC-1065-conjugates and related compounds for a selective cancer therapy Chen, Xiong 04 July 2006 (has links) No description available. 540 Chemie Mathematics and Computer Science CC-1065 Tetragastrin DNA-Binder Krebstherapie CC-1065 Tetragastrin DNA-binding cancer therapy 35.52 S
2	Development of prodrugs to deliver super-potent drugs to prostate tumours Twum, Elvis Asare January 2013 (has links) Conventional treatments for prostate cancer have significant limitations making it difficult to control the disease. Cyclopropabenzindoles (CBI) are more biologically potent, stable and synthetically accessible analogues of cyclopropapyrroloindole (CPI) anti-tumour antibiotics, such as duocarmycin-SA and CC1065. A polymeric prodrug carrying a CBI drug attached to the polymeric backbone through a PSA cleavable linker peptide has two modes of selectivity: activation by PSA and the EPR effect. To synthesise a 5-amino-seco-CBI analogue, 2,4-dinitronaphthalen- 1-ol gave di-Boc-1-iodonaphthalene-2,4-diamine in five steps (triflation, SNAr displacement with iodide, reduction (loss of iodine), protection and restoration of the iodine. For the amino-seco-CBI, it was important to discriminate between N2 and N4. Acidic removal of the Boc-group(s) resulted in deiodination. NMR investigations showed an unexpected Wheland-like cationic intermediate. N3 of naphthalene-1,3-diamine was selectively trifluoroacetylated and N1 was masked with Boc. Electrophilic iodination gave an orthogonally protected 1-iodonaphthalene-2,4-diamine. Allylation at the trifluoroacetamide was followed by free radical cyclisation with TEMPO trap. Removal of the trifluoroacetyl group allowed coupling to 5-(2-(dimethylamino)ethoxy)-1H-indole-2-carboxylic acid. Reductive removal of 2,2,6,6-tetramethylpiperidine, substitution of the exposed hydroxy group with chloride and removal of the Boc-group gave the amino-seco-CBI drug, 5-amino-1-chloromethyl-3-(5-(2-dimethylaminoethoxy)indole-2-carbonyl)-2,3-dihydro-1H-benz[e]indole. A DNA-melting assay confirmed that it binds very strongly to dsDNA causing a 13 deg. C increase in melting temperature. The drug was a highly potent cytotoxin in vitro, with IC50 = 18 nM against LNCaP prostate cancer cells. The polymeric prodrug system involved the synthesis of the pentapeptide SSKLQ. The amide side chain of glutamine can be masked as the nitrile and this can be quantitatively hydrated to the γ-carboxamide of L-Gln with hydroperoxide. The pentapeptide was coupled to 4-methoxynaphthalen-1-amine and to poly(ethylene glycol) as a model polymeric prodrug system. Efficient release of the model drug from the polymeric prodrug by PSA will allow this polymeric prodrug system to be adopted for the synthesised amino-seco-CBI drug. 616.99463061
3	Chemical and Biological Explorations of the Family of CC-1065 and the Duocarmycin Natural Products. Ghosh, Nandita, Sheldrake, Helen M., Searcey, M., Pors, Klaus 10 1900 (has links) yes / CC-1065, the duocarmycins and yatakemycin are members of a family of ultrapotent antitumour antibiotics that have been the subject of extensive investigations due to their mode of action and potential in the design of new anticancer therapeutics. The natural products and their analogues exert their effects through a sequence selective alkylation of duplex DNA in the minor groove at the N3 of adenine. An understanding of their structure and its effect on biological activity has been derived through chemical synthesis and has also generated new potential lead compounds. These studies form the first section of the review. The desire to progress these compounds to clinic has also led to studies of bioconjugation and prodrug formation and this is discussed in the second section of the review. The combination of synthesis with key biological experiments is a powerful tool to define the requirements for the development of natural products as potential therapeutic agents. The studies described herein form an excellent paradigm for the study and development of other natural products. / EPSRC, Yorkshire Cancer Research, Big C Cancer Research, UCB Pharma Duocarmycin Anti-tumour antibiotics CC-1065 Aadozelesin CBI CPI DNA minor groove binders (MGBs) Adenine N3 alkylation Prodrugs Anti-cancer therapeutics Natural products
4	Synthese und biologische Evaluierung von fluorezenzmarkierten Duocarmycin-Analoga / Synthesis and biological evaluation of fluorescence labeled Duocarmycin analogues Behrendt, Frank 25 November 2011 (has links) No description available. 540 Chemie Chemistry ADEPT Tumortherapie Prodrug CC-1065 Duocarmycine DNA Fluoreszenz Live Cell Imaging Zelluläre Aufnahme Wirkmechanismus ADEPT tumor therapy prodrug CC-1065 duocarmycin DNA fluorescence Live Cell Imaging Cellular Uptake mechanism of action 35.26 35.29 35.33 35.59 35.71 35.75 35.52 44.33
5	Synthese, biologische Evaluation und Untersuchung des Wirkmechanismus neuartiger Duocarmycin-Analoga für eine selektive Krebstherapie / Synthesis, Biological Evaluation and Investigation of the Mode of Action of Novel Anti-Tumour Agents for a Selective Cancer Therapy Krewer, Birgit 22 January 2009 (has links) No description available. 540 Chemie Mathematics and Computer Science ADEPT Tumortherapie Prodrug CC-1065 Duocarmycine DNA Massenspektrometrie Chromatographie Circular Dichroismus Wirkmechanismus ADEPT tumor therapy prodrug CC-1065 duocarmycin DNA mass spectrometry chromatography Circular Dichroism mechanism of action 35.26 35.29 35.33 35.59 35.71 35.75 35.52 44.33

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