Relationships between the structure of taxol analogues and their antimitotic activity

J Med Chem. 1991 Mar;34(3):992-8. doi: 10.1021/jm00107a017.

Abstract

A variety of synthetic analogues of taxol, a naturally occurring antitumor diterpene, were examined for their potency to inhibit microtubule disassembly. For some of the compounds, the in vitro cytotoxic properties showed a good correlation with the tubulin assay. This structure-activity relationship study shows that inhibition of microtubule disassembly is quite sensitive to the configuration at C-2' and C-3'. A correlation between the conformation of the side chain at C-13 and the activity is suggested. Of all the compounds examined, one of the most potent in inhibiting microtubule disassembly and in inhibiting murine P388 leukemic cells, N-debenzoyl-N-tert-(butoxycarbonyl)-10-deacetyltaxol, named taxotere, was selected for evaluation as a potential anticancer agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Brain / ultrastructure
  • Cell Division / drug effects
  • Chemical Phenomena
  • Chemistry
  • Leukemia P388 / pathology
  • Mice
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Molecular Conformation
  • Molecular Structure
  • Paclitaxel
  • Stereoisomerism
  • Structure-Activity Relationship
  • Swine
  • Tubulin / metabolism

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Tubulin
  • Paclitaxel