Synthesis, tubulin assembly, and antiproliferative activity against MCF7 and NCI/ADR-RES cancer cells of 10-O-acetyl-5'-hydroxybutitaxel

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6165-7. doi: 10.1016/j.bmcl.2008.10.010. Epub 2008 Oct 7.

Abstract

A highly efficient kinetic resolution of racemic cis-4-(2-tert-butyldimethylsilyloxy-1,1-dimethyl)ethyl-3-tert-butyldimethylsilyloxy-azetidin-2-one with 7-O-triethylsilylbaccatin III was carried out to furnish 10-O-acetyl-5'-hydroxybutitaxel after removal of the silyl protecting groups. The compound was 50% as active as paclitaxel in a tubulin assembly assay and showed significantly decreased activity against MCF7 cell proliferation compared to paclitaxel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Molecular Structure
  • Organosilicon Compounds / chemistry
  • Paclitaxel* / analogs & derivatives
  • Paclitaxel* / chemical synthesis
  • Paclitaxel* / chemistry
  • Paclitaxel* / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tubulin / drug effects*
  • Tubulin / metabolism
  • beta-Lactams / chemistry

Substances

  • 10-O-acetyl-5'-hydroxybutitaxel
  • Organosilicon Compounds
  • Tubulin
  • beta-Lactams
  • Paclitaxel