Synthesis and biological evaluation of novel analogues of dictyostatin

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Abstract

Novel analogues of the microtubule-stabilising agent dictyostatin were designed using existing SAR information from the structurally related discodermolide, synthesised by a late-stage diversification strategy and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including those known to exhibit Taxol-resistance (AsPC-1, DLD-1, PANC-1, NCI/ADR).

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Novel analogues of the microtubule-stabilising agent dictyostatin were designed, synthesised and evaluated in vitro for growth inhibition against a range of human cancer cell lines.

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Acknowledgments

NIH Grant No. CA-93455 provided financial support for the biological assays and general project support was provided by the EPSRC, AstraZeneca and the EC (Marie Curie Fellowship to K.G.P.). We thank Dr. John Leonard (AstraZeneca) for helpful discussions, Dr. Richard Isbrucker and Dr. Pat Linley (HBOI) for assisting in our biological evaluation and Dr. Stuart Mickel (Novartis) for the gift of chemicals.

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