Prodrug Mono Therapy: Synthesis and biological evaluation of an etoposide glucuronide-prodrug

A glucuronide-based prodrug of etoposide has been synthesized for a Prodrug Mono Therapy strategy. The aim is to selectively liberate the active compound by beta-D-glucuronidase already present in necrotic tumours. Outside from these sites, this enzyme is known to be localised inside the lysosomes. The three components of this prodrug are the glucuronic acid (substrate of the enzyme), the spacer (for a faster cleavage), and the active etoposide. In vitro, the prodrug was shown to be less cytotoxic and more water-soluble than etoposide itself. Finally, in the presence of the beta-D-glucuronidase, cleavage of the prodrug with complete release of the drug has been observed. (C) 2003 Elsevier Science Ltd. All rights reserved.