Synthesis and evaluation of taxol-folic acid conjugates as targeted antineoplastics

Bioorg Med Chem. 2002 Jul;10(7):2397-414. doi: 10.1016/s0968-0896(02)00019-6.

Abstract

A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid. One agent (54), further evaluated in animal studies was found to increase the lifespan in mice, but was less effective than Taxol itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Folic Acid / chemistry*
  • Humans
  • Hydrolysis
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry / methods
  • Paclitaxel / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Folic Acid
  • Paclitaxel