Synthesis, biological activity and receptor-based 3-D QSAR study of 3'-N-substituted-3'-N-debenzoylpaclitaxel analogues

Bioorg Med Chem. 2002 Oct;10(10):3135-43. doi: 10.1016/s0968-0896(02)00217-1.

Abstract

3'-N-Substituted-3'-N-debenzoylpaclitaxel analogues were synthesized and investigated for their 3-D QSAR by using comparative molecular field analysis (CoMFA). The CoMFA model obtained from receptor(microtubule)-paclitaxel binding structure displays an excellent predictive power to forecast the biological activity of new 3'-N-substituted-3'-N-debenzoylpaclitaxel analogues as well as the ability to explain the activity of the known paclitaxel analogues. The cross-validated r(2)(cv) values of the selected models are 0.835 and 0.616 for A549 and SK-OV-3, respectively, and the non-cross-validated r(2)(ncv) values of them are 0.992 and 0.974.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Humans
  • Microtubules / metabolism
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Quantitative Structure-Activity Relationship*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Paclitaxel