Glycosidase-activated prodrugs of a cytotoxic iron chelator for targeted cancer therapy

Abstract

New glycoside-prodrugs based on the iron chelator deferasirox were designed. Selective enzymatic activation by glycosidases was observed within 24 hours, accompanied by cancer cell-selective cytotoxicity. Notably, derivative 3a, bearing a β-D-galactose moiety, showed promising selective activity against galactosidase overexpressing OvCar-3 cells (IC50 9.1 ± 1.6 μM) while maintaining low activity against fibroblast control GM5756 cells (IC50 > 100 μM).

Graphical abstract: Glycosidase-activated prodrugs of a cytotoxic iron chelator for targeted cancer therapy

Supplementary files

Article information

Article type
Research Article
Submitted
14 Mar 2025
Accepted
25 May 2025
First published
19 Jun 2025
This article is Open Access
Creative Commons BY license

RSC Med. Chem., 2025, Advance Article

Glycosidase-activated prodrugs of a cytotoxic iron chelator for targeted cancer therapy

D. Tomar, A. Steinbrueck, A. C. Sedgwick, M. S. Levine, J. L. Sessler and N. Metzler-Nolte, RSC Med. Chem., 2025, Advance Article , DOI: 10.1039/D5MD00232J

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