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.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Chow MJ,Babak MV,Wong DY,Pastorin G,Gaiddon C,Ang WHdoi
10.1021/acs.molpharmaceut.6b00348subject
Has Abstractpub_date
2016-07-05 00:00:00pages
2543-54issue
7eissn
1543-8384issn
1543-8392journal_volume
13pub_type
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