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Content archived on 2024-06-18

Design, synthesis and biological studies of novel 1,4-benzoxazepines as antitumour compounds

Objective

Breast cancer remains the most common cancer in women and is the most frequent cause of cancer death. Over the past 20 years, the 5-year survival for patients with breast cancer has increased by around 10%, largely as a result of earlier diagnosis and better treatment. Nevertheless, 5-year survival rates for people with breast cancer range between 60% and 70%, and many patients still die from the disease. Although 5-fluorouracil (5-FU) was first introduced in 1957, it remains an essential part of the treatment of a wide range of solid tumours. Although this antimetabolite is toxic, its efficacy makes it one of the most widely used agents against solid tumours. 5-FU-containing acyclonucleosides have been reported to induce myogenic differentiation in rhabdomy osarcoma cells, suggesting that these drugs might be useful for differentiation therapy in this type of tumour. Such a therapy is an attractive approach to cancer treatment, which assumes that neoplastic transformation reveals the inability of a cell popul ation to couple proliferation and differentiation signals. Following these results a series of 1,4-benzoxazepines linked to natural or synthesised bases is proposed. A library of compounds will be synthesized in solid phase to rapidly obtain the maximum structural variety. The compounds will be tested as in vitro antiproliferative, apoptotic and cell cycle drug-acting agents against breast cancer. Biological studies will be carried out to determine the mechanism of action at the molecular level. QSAR, SAR and molecular modelling studies will be developed throughout the project. The information obtained from these structure-activity relationships will be valuable to determine which parts of the synthesized molecules are essentially involved in the activity and potency. The anticancer activity of the most potent and less toxic compounds will be assayed in mice.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-11
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERG - Marie Curie actions-European Re-integration Grants

Coordinator

UNIVERSIDAD DE GRANADA
EU contribution
No data
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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