Design, Synthesis, and Biological Evaluation of a Novel Water-soluble Prodrug of Docetaxel with Amino Acid as a Linker

Chem Biol Drug Des. 2016 Sep;88(3):363-9. doi: 10.1111/cbdd.12762. Epub 2016 May 24.

Abstract

The synthesis and preliminary evaluation of derivatives of docetaxel with novel amino acid as a linker named as LK-193˜LK-196 was described. The C2'-modified compound LK-196 behaves as a prodrug; that is, docetaxel is generated upon exposure to human plasma. The compound was also found to have greatly improved water solubility. The pharmacodynamic results showed LK-196 had the self-evident inhibitory effect on tumor growth in vivo, which is a promising candidate for further biological evaluation.

Keywords: Prodrug of docetaxel; biological evaluation; synthesis; water-soluble.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Docetaxel
  • Drug Design*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry*
  • Prodrugs / pharmacokinetics
  • Prodrugs / therapeutic use*
  • Rats, Sprague-Dawley
  • Solubility
  • Taxoids / chemical synthesis
  • Taxoids / chemistry*
  • Taxoids / pharmacokinetics
  • Taxoids / therapeutic use*
  • Water / chemistry

Substances

  • Antineoplastic Agents
  • Prodrugs
  • Taxoids
  • Water
  • Docetaxel