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Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
A new cyclopamine glucuronide prodrug with improved kinetics of drug release
Brigitte Renoux1, Thibaut Legigan, Souheyla Bensalma
1Université de Poitiers, UMR-CNRS 6514, 4 rue Michel Brunet, BP 633, 86022, Poitiers, France.
Abstract:
We prepared a new glucuronide prodrug of cyclopamine designed to target selectively the Hedgehog signalling pathway of cancer cells. This prodrug includes a novel self-immolative linker bearing a hydrophilic side chain that can be easily introduced via"click chemistry". With this design, the prodrug exhibits reduced toxicity compared to the free drug on U87 glioblastoma cells. However, in the presence of β-glucuronidase, the prodrug conducts to the quick release of cyclopamine thereby restoring its antiproliferative activity.
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