Novel microtubule-stabilising agents have great potential as cancer chemotherapeutic agents - where there is a need for improved pharmacological profiles, reduced side-effects, and efficacy against otherwise drug-resistant cancers. The 16-membered macrolid e peloruside A is a potent inhibitor of cancer cell proliferation at the nanomolar level. By sharing the same microtubule-stabilising mechanism as Taxol and retaining activity against multi drug-resistant cancer cells, peloruside A represents a potential ne w chemotherapeutic agent to the treatment of solid tumours. Due to the supply shortage from the sponge source, chemical total synthesis is essential for generating useful quantities of peloruside A to enable its pre-clinical development.
The primary objective of the proposed project is to develop a flexible and stereo-controlled synthesis of peloruside A, using methodology developed in the host group, in order to provide material for further biological evaluation. A secondary objective is the synthesis of simplified structural analogues, including hybrids with the epothilones, which would then be tested for tubulin binding and cytotoxicity to determine the essential structural characteristics for bioactivity.
The applicant will improve her research training and expand her knowledge and experience in the synthesis of biologically active molecules that may have therapeutic potential. 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 host scientist has exceptional experience in total synthesis and the development of new synthetic methods. The training/mobility period will provide a good synergy with the applicant and apos;s pre-doctoral training and offers an excellent research infrastructure.
Call for proposal
See other projects for this call