Synthesis and interactions of 7-deoxy-, 10-deacetoxy, and 10-deacetoxy-7-deoxypaclitaxel with NCI/ADR-RES cancer cells and bovine brain microvessel endothelial cells

Bioorg Med Chem Lett. 2006 Jan 15;16(2):433-6. doi: 10.1016/j.bmcl.2005.09.043. Epub 2005 Nov 3.

Abstract

7-Deoxypaclitaxel, 10-deacetoxypaclitaxel and 10-deacetoxy-7-deoxypaclitaxel were prepared and evaluated for their ability to promote assembly of tubulin into microtubules, their cytotoxicity against NCI/ADR-RES cells and for their interactions with P-glycoprotein in bovine brain microvessel endothelial cells. The three compounds were essentially equivalent to paclitaxel in cytotoxicity against NCI/ADR-RES cells. They also appeared to interact with P-glycoprotein in the endothelial cells with the two 10-deacetoxy compounds having less interaction than paclitaxel and 7-deoxypaclitaxel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / cytology
  • Brain / drug effects
  • Cattle
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Endothelial Cells / drug effects*
  • Humans
  • Molecular Conformation
  • Neoplasms, Experimental / drug therapy*
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemical synthesis
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Structure-Activity Relationship
  • Taxoids / chemical synthesis
  • Taxoids / chemistry
  • Taxoids / pharmacology

Substances

  • 10-deacetoxy-7-deoxypaclitaxel
  • 10-deacetoxypaclitaxel
  • 7-deoxypaclitaxel
  • Taxoids
  • Paclitaxel