Study of a cyclopamine glucuronide prodrug for the selective chemotherapy of glioblastoma

Florian Hamon; Brigitte Renoux; Corinne Chadéneau; Jean-Marc Muller; Sébastien Papot

doi:10.1016/j.ejmech.2009.12.067

Study of a cyclopamine glucuronide prodrug for the selective chemotherapy of glioblastoma

Eur J Med Chem. 2010 Apr;45(4):1678-82. doi: 10.1016/j.ejmech.2009.12.067. Epub 2010 Jan 13.

Authors

Florian Hamon¹, Brigitte Renoux, Corinne Chadéneau, Jean-Marc Muller, Sébastien Papot

Affiliation

¹ Université de Poitiers, UMR-CNRS 6514, 40 avenue du Recteur Pineau, 86022 Poitiers, France.

PMID: 20116904
DOI: 10.1016/j.ejmech.2009.12.067

Abstract

The first glucuronide prodrug of the hedgehog signaling inhibitor cyclopamine was synthesized. The carbamoyl derivatisation of cyclopamine significantly decreased its toxicity towards the U87 human glioblastoma cell line. However, when the prodrug was incubated with beta-glucuronidase in the culture media, the active drug was efficiently released thereby restoring its anti-proliferative activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / therapeutic use*
Brain Neoplasms / drug therapy*
Brain Neoplasms / pathology
Cell Line, Tumor
Chromatography, High Pressure Liquid
Glioblastoma / drug therapy*
Glioblastoma / pathology
Glucuronides / chemistry*
Humans
Magnetic Resonance Spectroscopy
Prodrugs / therapeutic use*
Spectrometry, Mass, Electrospray Ionization
Veratrum Alkaloids / chemistry
Veratrum Alkaloids / therapeutic use*

Substances

Antineoplastic Agents
Glucuronides
Prodrugs
Veratrum Alkaloids
cyclopamine