Objective The proposed research describes a strategy for the convergent synthesis of diazobenzofluorene containing antitumor antibiotics Lomaiviticins A and B as well as the structurally related Kinamycin C. They are potent DNA cleaving agents and exhibit remarkable activity against a broad spectrum of cancer cell lines. These structurally novel antitumor antibiotics have a unique cytotoxicity profile, compared to other known DNA-damaging anticancer drugs such as adriamycin and mitomycin C, which may suggest a different mechanism of interaction with DNA. However, the currently limited availability of these compounds isolated by fermentation and the present lack of any methodology to generate synthetic analogs could hamper further research in the analysis of these highly potent DNA-cleaving agents. Access to these natural products as well as their analogs by means of chemical synthesis, would enable the scientific community to elucidate their mode of action and the origin of their cytotoxicity. Thus, in the absence of an alternative state of the art and given the potential of these molecules to become therapeutic cancer agents, the main objectives of the proposed project are: a) the development of a synthetic methodology for the convergent synthesis of lomaiviticins and their analogs, b) extension of this methodology towards the synthesis of the structurally related antitumor antibiotic kinamycin C, and c) the design and synthesis of structurally diverse diazobenzo[a]fluorene analogs aiming to identify new cytotoxic agents and some of the structural features required for their biological activity. Fields of science natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsmedical and health sciencesclinical medicineoncologyengineering and technologyindustrial biotechnologybioprocessing technologiesfermentation Keywords Combinatorial chemistry Oncology Organic chemistry Pharmaceutical chemistry Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Call for proposal FP7-PEOPLE-2007-4-3-IRG See other projects for this call Funding Scheme MC-IRG - International Re-integration Grants (IRG) Coordinator PANEPISTIMIO IOANNINON EU contribution € 100 000,00 Address PANEPISTEMIOYPOLE PANEPISTEMIO IOANNINON 45110 Ioannina Greece See on map Region Βόρεια Ελλάδα Ήπειρος Ιωάννινα Activity type Higher or Secondary Education Establishments Administrative Contact Demosthenes Fokas (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
