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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.

SUBMITTER: Chen QH

PROVIDER: S-EPMC2790820 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Design, synthesis and biological evaluation of bridged epothilone D analogues.

Chen Qiao-Hong QH Ganesh Thota T Brodie Peggy P Slebodnick Carla C Jiang Yi Y Banerjee Abhijit A Bane Susan S Snyder James P JP Kingston David G I DG

Organic & biomolecular chemistry 20081106 24

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. ...[more]

PMID: 19039362

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