Halogenated indole-3-acetic acids as oxidatively activated prodrugs with potential for targeted cancer therapy

Bioorg Med Chem Lett. 2002 Sep 16;12(18):2523-6. doi: 10.1016/s0960-894x(02)00505-x.

Abstract

Substituted indole-3-acetic acid (IAA) derivatives, plant auxins with potential for use as prodrugs in enzyme-prodrug directed cancer therapies, were oxidised with horseradish peroxidase (HRP) and toxicity against V79 Chinese hamster lung fibroblasts was determined. Rate constants for oxidation by HRP compound I were also measured. Halogenated IAAs were found to be the most cytotoxic, with typical surviving fractions of <10(-3) after incubation for 2h with 100 microM prodrug and HRP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cricetinae
  • Halogens / chemistry*
  • Horseradish Peroxidase / metabolism
  • Indoleacetic Acids / chemistry*
  • Indoleacetic Acids / metabolism
  • Indoleacetic Acids / pharmacology*
  • Kinetics
  • Oxidation-Reduction
  • Prodrugs / chemistry*
  • Prodrugs / metabolism
  • Prodrugs / pharmacology*

Substances

  • Antineoplastic Agents
  • Halogens
  • Indoleacetic Acids
  • Prodrugs
  • indoleacetic acid
  • Horseradish Peroxidase