Abstract
The ligands L1 and L2 both form separable dinuclear double stranded helicate and mesocate complexes with Ru(II). In contrast to clinically approved platinates the helicate isomer of [Ru2(L1)2]4+ was preferentially cytotoxic to isogenic cells (HCT116 p53-/-) which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity with the achiral isomer being preferentially cytotoxic towards HCT116 p53+/+. Other structurally similar Ru(II)-containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be ‘tuned’ to either genotype. In the search for compounds that can target difficult to treat tumours that lack the p53 tumour suppressor gene, [Ru2(L1)2]4+ is a promising compound for further development.
Original language | English |
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Pages (from-to) | 9799-9804 |
Number of pages | 6 |
Journal | Angewandte Chemie - International Edition |
Volume | 57 |
Issue number | 31 |
Early online date | 4 Jun 2018 |
DOIs | |
Publication status | Published - 26 Jul 2018 |
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Jane Owen-Lynch
- Vice-Chancellor's Office - Pro Vice-Chancellor (Teaching and Learning)
- Department of Biological and Geographical Sciences
- Pharmacology and Therapeutics Centre - Associate Member
Person: Academic
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Roger Phillips
- Department of Pharmacy - Associate Dean of Research Innovation and Knowledge Exchange
- School of Applied Sciences
- Pharmacology and Therapeutics Centre - Director
- Cellular and Molecular Models of Disease Centre - Associate Membership
- Centre for Biomimetic Societal Futures
Person: Academic
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Craig Rice
- Department of Chemical Sciences - Professor and Head of Department of Chemistry
- School of Applied Sciences
- Structural, Molecular and Dynamic Modelling Centre - Director
Person: Academic