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Journal articles
Structural Determinants of p53-Independence in Anticancer Ruthenium-Arene Schiff-Base Complexes
Abstract : p53 is a key tumor suppressor gene involved in key cellular processes and implicated in cancer therapy. However, it is inactivated in more than 50% of all cancers due to mutation or overexpression of its negative regulators. This leads to drug resistance and poor chemotherapeutic outcome as most clinical drugs act via a p53-dependent mechanism of action. An attractive strategy to circumvent this resistance would be to identify new anticancer drugs that act via p53-independent mode of action. In the present study, we identified 9 Ru (II)-Arene Schiff-base (RAS) complexes able to induce p53-independent cytotoxicity and discuss structural features that are required for their p53-independent activity. Increasing hydrophobicity led to an increase in cellular accumulation in cells with a corresponding increase in efficacy. We further showed that all nine complexes demonstrated p53-independent activity. This was despite significant differences in their physicochemical properties, suggesting that the iminoquinoline ligand, a common structural feature for all the complexes, is required for the p53-independent activity.
Cited literature [56 references]
https://www.hal.inserm.fr/inserm-02365323
Contributor : Christian Gaiddon <>
Submitted on : Friday, November 15, 2019 - 1:14:32 PM
Last modification on : Saturday, November 16, 2019 - 1:30:39 AM
Document(s) archivé(s) le : Sunday, February 16, 2020 - 4:32:08 PM
Contributor : Christian Gaiddon <>
Submitted on : Friday, November 15, 2019 - 1:14:32 PM
Last modification on : Saturday, November 16, 2019 - 1:30:39 AM
Document(s) archivé(s) le : Sunday, February 16, 2020 - 4:32:08 PM
