Obiettivo Cancer continues to be an important public health concern and socio-economic problem. Among the most promising newly established drugs, palliate (Taxi) and docetaxel (Texture) have the broadest ant tumour spectra in the clinic and are used increasingly for the treatment of ovarian cancer and metastasis breast cancer, with promise also for the treatment of lung, skin, and head and neck cancers. However, this beneficial effect still remains hampered by many drawbacks. The major cellular target for palliate and other taxies is the protein tubule, whose polymerisation into microtubules is induced and stabilised, blocking the tumour cells in mitosis and preventing proliferation. Recently, several natural products isolated both from marine sources (soft corals or sponges) and from terrestrial bacteria have been reported to exert potent catatonic activity through a related-related mechanism. Among these, sarcodictyins A and B and eleutherobin (the " eleutheside" family of microtubule- stabilizing agents) are active against paclitaxel-resislant tumour cell lines and therefore hold potential as second generation microtubule-stabilizing anticancer drugs. Given the scarcity of the natural products, a practical total synthesis of the eleuthesides (amenable to large-scale preparation at a reasonable cost), and the synthesis of simplified eleutheside analogues, are still strongly desirable. The central aim of this project is to use the expertise gained within the group in the preparation of tri- substituted eleutheside analogues, and attempt the synthesis of: (a) a number of new eleutheside analogues functionalized at C-7; (b) the fully functionalised analogues, from which the Danishes key-intermediate (an advanced intermediate in the total synthesis of eleutherobin) could be easily obtained. Our plan is to screen these compounds both on biochemical tests, like tubule assembly, and on cellular tumour models. Campo scientifico medical and health scienceshealth sciencespublic healthnatural sciencesbiological sciencesmicrobiologyvirologymedical and health sciencesclinical medicineoncologybreast cancermedical and health sciencesclinical medicineoncologyhead and neck cancermedical and health sciencesbasic medicineimmunologyimmunotherapy Parole chiave microtubule microtubule-stabilizing anticancer drugs ring closing metathesis stabilizing anticancer drugs stereoselective synthesis synthesis Programma(i) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Argomento(i) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Invito a presentare proposte FP6-2002-MOBILITY-5 Vedi altri progetti per questo bando Meccanismo di finanziamento EIF - Marie Curie actions-Intra-European Fellowships Coordinatore UNIVERSITA DEGLI STUDI DI MILANO Contributo UE Nessun dato Indirizzo Via Festa Del Perdono 7 MILANO Italia Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato
