Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard.

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.

• Authors: S Papot, D Combaud, K Bosslet, M Gerken, J Czech, J P Gesson
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 10 Issue 16 Pg. 1835-7 (Aug 21 2000) ISSN: 0960-894X [Print] England
• PMID: 10969980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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