Glycosidase-activated prodrugs of a cytotoxic iron chelator for targeted cancer therapy
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 (IC<sub>50</sub> 9.1 ± 1.6 μM) while maintaining low activity against fibroblast control GM5756 cells (IC<sub>50</sub> > 100 μM).
Authors
- Jonathan L. Sessler (ORCID: https://orcid.org/0000-0002-9576-1325)
- Axel Steinbrueck (ORCID: https://orcid.org/0000-0001-6014-3204)
- Matthew S. Levine (ORCID: https://orcid.org/0000-0002-2622-2678)
- Adam C. Sedgwick (ORCID: https://orcid.org/0000-0002-3132-2913)
- Nils Metzler‐Nolte (ORCID: https://orcid.org/0000-0001-8111-9959)
- Deepak Tomar (ORCID: https://orcid.org/0000-0001-7633-5657)
Institutions
- King's College London (GB)
- The University of Texas at Austin (US)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- RSC Medicinal Chemistry
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d5md00232j
- Primary Topic
- Biochemical and Molecular Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Welch Foundation
- King’s College London
- King's College London
- Deutsche Forschungsgemeinschaft