Synthesis and biological evaluation of 2-acyl analogues of paclitaxel (Taxol)

J Med Chem. 1998 Sep 10;41(19):3715-26. doi: 10.1021/jm980229d.

Abstract

The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines with tubulin polymerization activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic* / chemical synthesis
  • Antineoplastic Agents, Phytogenic* / chemistry
  • Antineoplastic Agents, Phytogenic* / pharmacology
  • Biopolymers
  • Catalysis
  • Cell Division / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Paclitaxel* / analogs & derivatives
  • Paclitaxel* / chemical synthesis
  • Paclitaxel* / chemistry
  • Paclitaxel* / pharmacology
  • Polyethylene Glycols / chemistry
  • Structure-Activity Relationship
  • Tubulin / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Biopolymers
  • Tubulin
  • Polyethylene Glycols
  • Paclitaxel