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Content archived on 2024-06-18

Synthesis and Biological Target Identification of the Potent Tubulin Inhibitor Disorazole C1 and Novel Heterocyclic Analogues

Objective

"Cancer is a common and life-threatening disease with world-wide occurrence, and the number of affected individuals and morbidity continues to increase annually. It is therefore of great importance that straightforward syntheses of potential anti-cancer agents are developed in order to advance treatment and drug discovery in this field. The disorazoles, the subject of this proposal, are a group of natural products which display strong anticancer activity against a variety of cell lines, including multidrug resistant cells. Although one total synthesis and several approaches have been published towards the key family member disorazole C1, these are lengthy and poor-yielding. Consequently, a more-detailed investigation of the mode of action of this highly potent tubulin inhibitor has been severely hampered. The synthetic approach outlined in this proposal will dramatically increase the convergency of synthesis and will allow us to explore how changes in one of the key structural features affects the natural product structure and function. Working in the Hulme group laboratories, the Fellow will synthesise the disorazole C1 analogues with a pioneering approach to construction of the macrolactone core. Using computational modelling and a range of traditional and cutting-edge technologies (X-Ray, NMR and IM-MS) he will study the analogues' structures and tubulin-binding abilities. The Fellow will conduct biological tests including cell-based assays in-house, exploiting the world-leading expertise and facilities within EaStCHEM. The project is thus ideally placed to offer the Fellow a broad interdisciplinary training and give him new insights into both traditional and modern chemical biology and medicinal chemistry techniques. He will attend a series of training courses, tutor and lecture to undergraduates, and exercise considerable supervisory responsibility within the research group; thus enhancing his long-term prospects of becoming an independent academic researcher."

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2011-IEF
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.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE UNIVERSITY OF EDINBURGH
EU contribution
€ 209 033,40
Address
OLD COLLEGE, SOUTH BRIDGE
EH8 9YL Edinburgh
United Kingdom

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Region
Scotland Eastern Scotland Edinburgh
Activity type
Higher or Secondary Education Establishments
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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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