Prodrug Mono therapy: synthesis and biological evaluation of an etoposide glucuronide-prodrug Original Research Article

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 β-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 β-d-glucuronidase, cleavage of the prodrug with complete release of the drug has been observed.