Relationship between the structures of taxane derivatives and their microtubule polymerization activity

Biosci Biotechnol Biochem. 2012;76(2):349-52. doi: 10.1271/bbb.110797. Epub 2012 Feb 7.

Abstract

Paclitaxel (Taxol), one of the most potent anticancer drugs, is a microtubule-stabilizing compound that inhibits microtubule depolymerization within the cell. The structure of paclitaxel is composed of two key elements, a taxane ring and an N-benzoylphenylisoserine side chain at C-13. A number of natural and artificial compounds with taxane skeletons have been isolated, but almost none of their bioactivities have been evaluated. In this study, we focused on compounds having a taxane skeleton structure and examined their effects on tubulin dynamics. Although none of these compounds had an N-benzoylphenylisoserine side chain, three were found to promote tubulin assembly. On the other hand, one compound inhibited tubluin assembly in a way similar to nocodazole. These compounds exhibited novel structure-activity relationships of taxane compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents
  • Bridged-Ring Compounds / chemistry*
  • Bridged-Ring Compounds / pharmacology*
  • Humans
  • Microtubules / drug effects*
  • Microtubules / metabolism
  • Molecular Structure
  • Nocodazole
  • Paclitaxel
  • Polymerization
  • Structure-Activity Relationship
  • Taxoids / chemistry*
  • Taxoids / pharmacology*
  • Tubulin

Substances

  • Antineoplastic Agents
  • Bridged-Ring Compounds
  • Taxoids
  • Tubulin
  • taxane
  • Paclitaxel
  • Nocodazole