Synthesis and bioactivity of 2,4-diacyl analogues of paclitaxel

Bioorg Med Chem. 2001 Jan;9(1):171-8. doi: 10.1016/s0968-0896(00)00233-9.

Abstract

The 2,4-diacyl paclitaxel analogues 8a-8r were prepared from paclitaxel by acylation of 4-deacetyl-2-debenzoylpaclitaxel 1,2-carbonate (3) followed either by hydrolysis of the carbonate and acylation or by direct treatment of the carbonate with an aryllithium. Some of the resulting derivatives showed significantly improved tubulin assembly activity and cytotoxicity as compared with paclitaxel; in some cases this improvement was especially significant for paclitaxel-resistant cell lines.

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*
  • Cell Survival
  • Humans
  • Microtubule-Associated Proteins / biosynthesis
  • Molecular Structure
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / chemical synthesis
  • Paclitaxel / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Microtubule-Associated Proteins
  • Paclitaxel