In‐cell Catalysis by Tethered Organo−Osmium Complexes Generates Selectivity for Breast Cancer Cells
Abstract: Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi‐targeting strategy to overcome drug resistance. Nonetheless, many in‐cell catalysts in development are hindered by deactivation by endogenous nucleophiles. We have synthesised a highly potent, stable Os‐based 16‐electron half‐sandwich (‘piano stool’) catalyst by introducing a permanent covalent tether between the arene and chelated diamine ligand. This catalyst exhibits antiproliferative activity comparable to the clinical drug cisplatin towards triple‐negative breast cancer cells and can overcome tamoxifen resistance. Speciation experiments revealed Os to be almost exclusively albumin‐bound in the extracellular medium, while cellular accumulation studies identified an energy‐dependent, protein‐mediated Os accumulation pathway, consistent with albumin‐mediated uptake. Importantly, the tethered Os complex was active for in‐cell transfer hydrogenation catalysis, initiated by co‐administration of a non‐toxic dose of sodium formate as a source of hydride, indicating that the Os catalyst is delivered to the cytosol of cancer cells intact. The mechanism of action involves the generation of reactive oxygen species (ROS), thus exploiting the inherent redox vulnerability of cancer cells, accompanied by selectivity for cancerous cells over non‐tumorigenic cells.
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Bibliographic citation
-
In‐cell Catalysis by Tethered Organo−Osmium Complexes Generates Selectivity for Breast Cancer Cells ; day:09 ; month:07 ; year:2024 ; extent:12
ChemBioChem ; (09.07.2024) (gesamt 12)
- Creator
-
Coverdale, J. P. C.
Bedford, R. A.
Carter, O. W. L.
Cao, S.
Wills, M.
Sadler, P. J.
- DOI
-
10.1002/cbic.202400374
- URN
-
urn:nbn:de:101:1-2407101408522.503929209090
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:46 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Coverdale, J. P. C.
- Bedford, R. A.
- Carter, O. W. L.
- Cao, S.
- Wills, M.
- Sadler, P. J.
Other Objects (12)
In‐Cell Activation of Organo‐Osmium (II) Anticancer Complexes
In‐Cell Activation of Organo‐Osmium (II) Anticancer Complexes
Osmium
Osmium
44 Osmium.
XXIX. Osmium.
2. Osmium.
Osmium-Lampe
Talilmogene Iaherparepvec generates systemic T-cell-mediated anti-tumor immunity
In vitro osteoblastic differentiation of mesenchymal stem cells generates cell layers with distinct properties
Synergic Deprotonation Generates Alkali‐Metal Salts of Tethered Fluorenide‐NHC Ligands Co‐Complexed to Alkali‐Metal Amides
Sodium selectivity of Reissner's membrane epithelial cells
In‐Cell Activation of Organo‐Osmium (II) Anticancer Complexes
In‐Cell Activation of Organo‐Osmium (II) Anticancer Complexes
Osmium
Osmium
44 Osmium.
XXIX. Osmium.
2. Osmium.
Osmium-Lampe
Talilmogene Iaherparepvec generates systemic T-cell-mediated anti-tumor immunity
In vitro osteoblastic differentiation of mesenchymal stem cells generates cell layers with distinct properties
Synergic Deprotonation Generates Alkali‐Metal Salts of Tethered Fluorenide‐NHC Ligands Co‐Complexed to Alkali‐Metal Amides
Sodium selectivity of Reissner's membrane epithelial cells
In‐Cell Activation of Organo‐Osmium (II) Anticancer Complexes
In‐Cell Activation of Organo‐Osmium (II) Anticancer Complexes
Osmium
Osmium
44 Osmium.
XXIX. Osmium.
2. Osmium.
Osmium-Lampe
Talilmogene Iaherparepvec generates systemic T-cell-mediated anti-tumor immunity
In vitro osteoblastic differentiation of mesenchymal stem cells generates cell layers with distinct properties
Synergic Deprotonation Generates Alkali‐Metal Salts of Tethered Fluorenide‐NHC Ligands Co‐Complexed to Alkali‐Metal Amides