title: Design, synthesis and biological evaluation of bridged epothilone D analogues.
abstract: Six epothilone D analogues with a bridge between the C4-methyl and the C12-methyl carbons were prepared in an attempt to constrain epothilone D to its proposed tubulin-binding conformation. Ring-closing metathesis (RCM) was employed as the key step to build the C4-C26 bridge. In antiproliferative assays in the human ovarian cancer (A2780) and prostate cancer (PC3) cell lines, and also in tubulin assembly assay, all these compounds proved to be less active than epothilone D.
authors.affiliation: Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA. qchen06@vt.edu
authors.forename: Qiao-Hong
authors.initials: QH
authors.lastname: Chen
authors.forename: Thota
authors.initials: T
authors.lastname: Ganesh
authors.forename: Peggy
authors.initials: P
authors.lastname: Brodie
authors.forename: Carla
authors.initials: C
authors.lastname: Slebodnick
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Abhijit
authors.initials: A
authors.lastname: Banerjee
authors.forename: Susan
authors.initials: S
authors.lastname: Bane
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
authors.forename: David G I
authors.initials: DG
authors.lastname: Kingston
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D014404:Tubulin; C114026:desoxyepothilone B