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Synthesis of Marine Macrolides and Hybrid Structures as Novel Microtubule Stabilising Anticancer Agents


Project Summary and Research Objectives: Dictyostatin is a potent inhibitor of cell proliferation at the Nan molar level, causing cell cycle arrest at the G2/M phase and inducing apoptosis. By sharing the same microtubule-stabilising mechanism as the anticancer drug Taxi, and retaining activity against Resistant-resistant cancer cells, the marine microcline dictyostatin is a potential new chemotherapeutic agent for the treatment of solid tumours. Due to the extremely low isolation yield from the natural sponge source, total synthesis is essential for generating useful quantities of dictyostatin and determining the full structure. The main objective is to develop a flexible and modular synthesis of the 22-member microcline dictyostatin, using methodology developed in the host group, enabling the determination of the configuration at the 11 estrogenic centres and providing material for further biological evaluation. A secondary objective is the synthesis of novel microcline analogues and hybrid structures, which would be tested for tubule bundling and cytotoxicity. Expected Benefits: The researcher will benefit by improving her research training and by expanding her knowledge and experience in the synthesis of biologically active molecules that may have therapeutic potential, a field that she wishes to pursue after postdoctoral work. Not only will there be opportunities to learn and develop new synthetic methodologies, but also to participate in multidisciplinary research at the interface of chemistry, biology and medicine. The Chemistry Department of Cambridge University is a world-renowned institution and the scientist in charge has exceptional experience in the total synthesis of biologically important compounds, particularly anticancer agents, and the development of new synthetic methods, and has extensive international collaborations.

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The Old Schools, Trinity Lane
United Kingdom

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