Doxorubicin prodrugs with reduced cytotoxicity suited for tumour-specific activation

Anticancer Drug Des. 1998 Dec;13(8):955-68.

Abstract

The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-nitrophenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronate (5) and doxorubicin. Their low cytotoxicity, efficient release of doxorubicin after hydrolysis by beta-D-glucuronidase, and in the cases of 2 and 3 stability at pH 7.2 fulfil the preliminary requirement for their use in antibody-directed enzyme prodrug therapy or prodrug monotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / chemistry*
  • Antibiotics, Antineoplastic / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Chromatography, High Pressure Liquid
  • Doxorubicin / chemistry*
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Screening Assays, Antitumor
  • Drug Stability
  • Hydrolysis
  • Prodrugs / chemical synthesis*
  • Prodrugs / metabolism
  • Prodrugs / pharmacology
  • Tumor Cells, Cultured / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Prodrugs
  • Doxorubicin