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Design and synthesis of novel analogues of laulimalide as improved microtubule-stabilising anti-cancer agents

Objective

Despite considerable progress in cancer treatment, there is still a need for novel chemotherapeutic agents with improved pharmacological properties, reduced side-effects and efficacy against otherwise drug-resistant cancers. Laulimalide is a highly potent antimitotic agent, isolated from marine sponges, which inhibits the proliferation of cancer cell lines at the low nanomolar level. By sharing the same microtubule-stabilising mechanism as Taxol® and retaining activity against multidrug-resistant cancer cells, laulimalide presents a promising lead structure for the development of a new class of anti-cancer agents. In the proposed project, structurally simplified analogues of laulimalide will be designed and synthesised in order to investigate structure-activity relationships and the mechanism of action, as well as improving the chemical stability. In this context, the preferred bioactive conformation of laulimalide will be probed and the structural requirements for potent cytotoxicity explored.

The applicant will improve her research training and expand her knowledge in the synthesis of biologically active molecules with therapeutic potential, at the same time participating in multidisciplinary research at the interface of chemistry, biology and medicine. Moreover, she will work on a totally different topic from her PhD studies and thus acquire new knowledge and expertise. These additional skills and complementary experiences will lead in turn to an exceptionally well-trained researcher, with enhanced profess ional maturity and independence, providing lasting long-term benefits in her future career. In addition to the high scientific standards provided by this postdoctoral research experience, the fellow would profit from the excellent infrastructure and the opportunities to interact with leading scientists & young researchers of varying disciplines and nationalities, as well as collaborations with research groups in universities & industry with balancing expertise.

Field of science

  • /medical and health sciences/clinical medicine/cancer

Call for proposal

FP6-2002-MOBILITY-5
See other projects for this call

Funding Scheme

EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE