Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard

Bioorg Med Chem Lett. 2000 Aug 21;10(16):1835-7. doi: 10.1016/s0960-894x(00)00353-x.

Abstract

A new glucuronylated prodrug of nornitrogen mustard, incorporating the same spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower cytotoxicity against LoVo cancer cells is observed compared to the nornitrogen mustard alone. This is explained by cyclization of the intermediate carbamic acid to the inactive chloroethyl oxazolidinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Colonic Neoplasms
  • Cyclization
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Escherichia coli / enzymology
  • Glucuronates / chemical synthesis*
  • Glucuronates / chemistry
  • Glucuronates / pharmacology
  • Glucuronidase / chemistry
  • Glucuronidase / metabolism
  • Humans
  • Molecular Structure
  • Nitrogen Mustard Compounds / chemical synthesis*
  • Nitrogen Mustard Compounds / chemistry
  • Nitrogen Mustard Compounds / pharmacology
  • Oxazolidinones / chemistry
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Glucuronates
  • Nitrogen Mustard Compounds
  • Oxazolidinones
  • Prodrugs
  • Glucuronidase
  • nornitrogen mustard