title: Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Chemistry The Skaggs Institute for Chemical Biology The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. kcn@scripps.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.forename: M R
authors.initials: MR
authors.lastname: Finlay
authors.forename: S
authors.initials: S
authors.lastname: Ninkovic
authors.forename: N P
authors.initials: NP
authors.lastname: King
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Sarabia
authors.forename: D
authors.initials: D
authors.lastname: Vourloumis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D034261:Epothilones; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014404:Tubulin / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C113666:C12,13-cyclopropylepothilone A; D034261:Epothilones; D007783:Lactones; D013844:Thiazoles; D014404:Tubulin