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Chem Biol. 1998 Jul;5(7):365-72.

Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.

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Department of Chemistry The Skaggs Institute for Chemical Biology The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.



The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority.


The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified.


The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.

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